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[[Chronic Fatigue Syndrome]] (CFS) is also known as [[Myalgic Encephalomyelitis]] (ME) or [[ME/CFS]]. [[Chronic fatigue]] is a symptom of many diseases, illnesses, depression and drug therapies and the term is not interchangeable with the grossly misnamed disease [[CFS]]. There are many clinical and research definitions which create confusion for doctors, researchers, and patients. ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Defintions of ME and CFS].
{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
[[Chronic Fatigue Syndrome|Chronic fatigue syndrome]] (CFS) is also known as [[myalgic encephalomyelitis]] (ME) or [[ME/CFS]]. There are many [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome| clinical and research definitions]], which creates confusion for doctors, researchers, and patients.
 
It is worth noting that [[chronic fatigue]] (without the "syndrome") is a not a disease in and of itself, but a symptom of many diseases and drug therapies. This term is not interchangeable with [[Chronic fatigue syndrome|CFS]], [[Myalgic encephalomyelitis|ME]], or [[ME/CFS]].
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>
 
The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name="CDC-symptoms">{{Cite web | title = Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=[[Centers for Disease Control and Prevention]] | date = 2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref name="IOM2015-clinicians">{{Cite web|url=https://www.nap.edu/resource/19012/MECFScliniciansguide.pdf | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness {{!}} Clinicians' Guide | last = | first = | date = 2015 | website = National Academies|archive-url=|archive-date=|access-date= | authorlink =  | pages = 9-10}}</ref> A person with ME is likely to have other symptoms as well.<ref name="whatis" /> [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name="DiagnosticAlgorithm">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm | last = | first = | authorlink =  | date = 2015 | website = nationalacademies.org|archive-url=|archive-date=|access-date=}}</ref><ref name="IOM2015-clinicians" />. The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms along with additional [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], and [[immune system|immune]] symptoms.<ref name="Carruthers, 2003">{{Cite journal | last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers | last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson | last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner | last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested | last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry | last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi | last10 = Powles | first10 = AC Peter | authorlink10 = A C Peter Powles | last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey | last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols | journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 |  pages = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf }}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/genitourinary impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name="ICC2011criteria">{{Cite journal | last = Carruthers | first = Bruce M. | author-link = Bruce Carruthers | last2 = van de Sande | first2 = Marjorie I. | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Klimas | first4 = Nancy G. | author-link4 = Nancy Klimas | last5 = Broderick | first5 = Gordon | author-link5 = Gordon Broderick | last6 = Mitchell | first6 = Terry | authorlink6 = Terry Mitchell | last7 = Staines | first7 = Donald | author-link7 = Donald Staines | last8 = Powles | first8 = A.C. Peter | author-link8 = A C Peter Powles | last9 = Speight | first9 = Nigel | authorlink9 = Nigel Speight | last10 = Vallings | first10 = Rosamund | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = Lucinda | authorlink11 = Lucinda Bateman | last12 = Baumgarten-Austrheim | first12 = Barbara | authorlink12 = Barbara Baumgarten-Austrheim | last13 = Bell | first13 = David | author-link13 = David Bell | last14 = Carlo-Stella | first14 = Nicoletta | author-link14 = Nicoletta Carlo-Stella | last15 = Chia | first15 = John | author-link15 = John Chia | last16 = Darragh | first16 = Austin | author-link16 = Austin Darragh | last17 = Jo | first17 = Daehyun | author-link17 = Daehyun Jo | last18 = Lewis | first18 = Donald | author-link18 = Donald Lewis | last19 = Light | first19 = Alan | author-link19 = Alan Light | last20 = Marshall-Gradisnik | first20 = Sonya | author-link20 = Sonya Marshall-Gradisnik | last21 = Mena | first21 = Ismael | author-link21 = Ismael Mena | last22 = Mikovits | first22 = Judy | author-link22 = Judy Mikovits | last23 = Miwa | first23 = Kunihisa | author-link23 = Kunihisa Miwa | last24 = Murovska | first24 = Modra | author-link24 = Modra Murovska | last25 = Pall | first25 = Martin | author-link25 = Martin Pall | last26 = Stevens | first26 = Staci | author-link26 = Staci Stevens | date = 2011-08-22 | title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
 
Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal | last = Fukuda | first = K. | author-link = Keiji Fukuda | last2 = Straus | first2 = S.E. | authorlink2 = Stephen Straus | last3 = Hickie | first3 = I. | authorlink3 = Ian Hickie | last4 = Sharpe | first4 = M.C. | authorlink4 = Michael Sharpe | last5 = Dobbins | first5 = J.G. | authorlink5 = James Dobbins | last6 = Komaroff | first6 = A. | authorlink6 = Anthony Komaroff | date = 1994-12-15 | title = The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group | url = https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12 | pages = 953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":02">{{Cite journal | last = Sharpe | first = M C | last2 = Archard | first2 = L C | last3 = Banatvala | first3 = J E | last4 = Borysiewicz | first4 = L K | last5 = Clare | first5 = A W | last6 = David | first6 = A | last7 = Edwards | first7  = RH | last8 = Hawton | first8  = KE | last9 = Lambert | first9  = HP  | date = Feb 1991 | title = A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|volume=84|issue=2|pages=118–121|issn=0141-0768|pmc=1293107|pmid=1999813}}</ref> have been used for diagnosing CFS, they are broader criteria, making [[misdiagnosis of myalgic encephalomyelitis and chronic fatigue syndrome|misdiagnosis]] a concern.<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like | title = What Does a True ME Definition Look Like? | last = | first = |website=MEadvocacy.org|access-date=2019-01-25}}</ref><ref name="fukuda1994" /><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/ | title = AHRQ Evidence Review Changes Its Conclusions | last = Spotila | first=Jennie | authorlink=Jennie Spotila | last2 = Dimmock | first2 = Mary | authorlink2 = Mary Dimmock | date = 2016-08-16 | website = occupyme.net|archive-url=|archive-date=|access-date=2019-01-25}}</ref> There have been media reports of athletes diagnosed with [[myalgic encephalomyelitis]] (ME) or [[chronic fatigue syndrome]] (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes;<ref name=":7">{{Cite news |url = https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ | title = Marathon runner forced to quit work after developing ME claims diet change gave him his life back | first = Claudia | last = Tanner|publisher =iNews | date = 2018}}</ref><ref name=":8">{{Cite news | url=https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 | title = Muslim fighter with ME who left an arranged marriage to win world | last = Broadbent | first = Rick | date = 2017-12-02|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|language=en|issn=0140-0460|quote=}}</ref><ref name=":9">{{Cite news | url=http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 |at=6mins 18s| title = Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments|publisher=ABC News | first =Andy|last = Park | first2 = Clare | last2 = O'Halloran}}</ref><ref name=":10">{{Cite news | url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx | title = Nathan Douglas: London 2012 was the darkest period of my life | last = Broadbent | first = Rick | date = 2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|language=en|issn=0140-0460|quote=}}</ref> these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME or CFS.<ref name="spence">{{Cite web | last = Spence | first = Vance | authorlink = Vance Spence|website=Irish M.E. Association| title = Snippets {{!}} A presentation by MERGE Chairman Dr Vance Spence on 12 November 2005 at the Oak Tree Court Conference Centre, Coventry, at the invitation of the Warwickshire Network for ME|url = https://www.imet.ie/imet_website/snippets/7th_december_2005_snippets.html}}</ref> Some people with [[anemia]], [[allergy|allergies]], [[idiopathic chronic fatigue]] or [[:Category:Potential comorbidities|other fatiguing illnesses]] are erroneously diagnosed with CFS.<ref name="Carruthers, 2003" />
 
The acronym ME/CFS is widely used in research, by clinicians, patient organizations, and patients.
 
"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/ | title = Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society | last = | first = | date = |website=[[American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society]]|language=en-US|archive-url=|archive-date=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal | last= Jason | first = Leonard | last2 = Taylor | first2 = R.R. | last3 = Kennedy | first3 = C.L. | last4 = Song | first4 = S | last5 = Johnson | first5 = D | last6 = Torres | first6 = S.R. | date = 2001-01-01 | title = Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal | last = Natelson | first = Benjamin H. | date = 2019-02-19 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=41|issue=4 | pages = 612|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>
 
Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. As of 2021 the GET has been scrapped in the UK [https://www.theguardian.com/society/2021/oct/29/health-watchdog-nice-publishes-delayed-me-guidance].
 
The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a '''biological illness''', not a psychologic disorder" and impacts multiple body systems.<ref name="etiology" /> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name="CDC-symptoms" /> and says [[ME/CFS]] is a "disabling and complex disease."<ref name="what-is">{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html | title = What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-12}}</ref> 
 
[[File:SEID algorithm.JPG|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]


== Disease onset and course of illness==
== Disease onset and course of illness==
The disease [[ME/CFS]] is diagnosed when a person does not recover from a flu-like illness, [[EBV]], [[Mononucleosis]], [[HHV]], [[Q fever]], [[Virus]] or other infections and meets one or more diagnostic criteria for either ME, CFS or ME/CFS.<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref><ref>[http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS - MEpedia]</ref> "Occasionally,  ME/CFS has been triggered by environmental toxins, the receipt of an immunizing injection, or surviving a major trauma."<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Patient health is never the same and they experience numerous symptoms and disease severity which fluctuate day to day, week to week, month to month, year to year and decade to decade as well as varying symptoms and disease severity among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>  
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu2019">{{Cite journal | last = Chu | first = Lily | authorlink = Lily Chu | last2 = Valencia | first2 = Ian J. | authorlink2 = Ian Valencia | last3 = Garvert | first3 = Donn W. | authorlink3 = | last4 = Montoya | first4 = Jose G. | authorlink4 = Jose Montoya | authorlink5 =  | date = Jan 14, 2019 | title = Onset patterns and course of myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergies|allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf | title = CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education | last = | first = | authorlink =  | date = |website=cdc.gov | page = 6|archive-url=|archive-date=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu2019" /><ref name="CDC-pres">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html | title = Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS | date = 2018-12-12 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name="Evans2018">{{Cite journal | last = Evans | first = Meredyth | authorlink = Meredyth Evans | last2 = Jason | first2 = Leonard | author-link2 = Leonard Jason | date = 2018 | title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=}}</ref>
 
The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>
 
The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting body chemistry, changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref name="CDC-causes">{{Cite web | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=[[Centers for Disease Control and Prevention]] | date = 2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name="etiology" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or heart rate regulation.<ref name="etiology" />
=== Not a mental health disorder ===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name="etiology" />  


=== Pediatric ME/CFS ===
===No clear evidence that ME/CFS is contagious===
Children are also afflicted with ME/CFS.<ref>[http://www.openmedicinefoundation.org/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/ ME/CFS in Children - by David S. Bell, MD - Open Medicine Foundation]</ref><ref>[https://www.masscfids.org/pediatric-me-cfs-links Pediatric ME/CFS - Massachusetts CFIDS/ME FM Association]</ref> ''See'': [[Pediatric]].
[[:Category:Infectious agents|Infectious episodes]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf | title = CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education | last = | first = | authorlink =  | date = |website=CDC | page = 6|archive-url=|archive-date=|access-date=}}</ref> Nowadays, the vast majority of ME/CFS cases are sporadic rather than epidemic, and although some outbreaks have been caused by known viruses - such as the [[2003 Hong Kong outbreak|SARS pandemic]] and [[2019 Coronavirus pandemic outbreak|COVID-19]] - there is no clear evidence that sporadic ME/CFS cases are contagious.<ref name="pediatricprimer">{{Cite journal | last = Rowe | first = Katherine S. | last2 = Vallings | first2 = Rosamund | last3 = Stewart | first3 = Julian M. | last4 = Speight | first4 = Nigel | last5 = Schwartz | first5 = Malcolm S. | last6 = Medow | first6 = Marvin S. | last7 = Gurwitt | first7 = Alan | last8 = Friedman | first8 = Kenneth J. | last9 = Underhill | first9 = Rosemary A. | date = 2017 | title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer |url = https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref>


=== Prognosis ===
Families, partners, and friends do not report contracting ME/CFS from someone with the disease nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/ | title = Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> However, Underhill and O'Gorman (2006) researched 219 patients with ME/CFS, and concluded that close household contact and genetics were both risk factors for CFS, finding 3.2% of spouses/partners of those with CFS also had the illness.<ref name="UnderhillInfectious">{{Cite journal | last = Underhill | first = Rosemary A. | last2 = O'Gorman | first2 = Ruth | date = 2006-01-01 | title = Prevalence of Chronic Fatigue Syndrome and Chronic Fatigue Within Families of CFS Patients|url=https://doi.org/10.1300/J092v13n01_02|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1|pages=3–13|doi=10.1300/J092v13n01_02|issn=1057-3321}}</ref> This was a higher prevalence than all genetic relatives except children of patients. Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a line of research recommended by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-02-13}}</ref><br />
Prognosis for ME/CFS is generally poor. ''See'': [[Prognosis]]


=== Female to male ratio ===
[[Michael Sikora]] and collaborators at the [[Open Medicine Foundation]] hope that their research on the role of [[T cell]]s and immune-related [[Genetics of chronic fatigue syndrome|genes]] will help address "whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system".<ref name="omf-funded">{{Cite web|url=https://www.omf.ngo/2018/06/04/omf-funded-research/ | title = OMF funded research | date = Jun 4, 2018 | website = [[Open Medicine Foundation]]}}</ref>
Like many auto-immune and neuro-immune diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio is 6:1.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/21244747 Chronic fatigue syndrome/myalgic encephalomyelitis: an update. - PUBMed Dec. 2010]</ref> [[Fibromyalgia]] has a F/M 7:1 ratio<ref>[http://emedicine.medscape.com/article/329838-overview#a5 Fibromyalgia:Epidemiology - Medscape]</ref> and some ME/CFS patients have this additional diagnosis.<ref>[http://www.cdc.gov/arthritis/basics/fibromyalgia.htm Fibromyalgia - CDC]</ref><ref>[http://solvecfs.org/what-is-mecfs/ What Is ME/CFS (Fibromyalgia) Solve ME/CFS Initiative]</ref>
====Blood donation and organ transplant====
Patients with ME/CFS are banned from [[Blood donation|donating blood]] or tissues in the [[United Kingdom|UK]] by the UK's [[National Health Service]], including patients who have recovered.<ref name="Blood">{{Cite web|url=https://my.blood.co.uk/knowledgebase/Index/C | title = My Donor Record - Health, Eligibility & Travel|website=my.blood.co.uk|access-date=2021-04-01}}</ref><ref>{{Cite web|url=https://transfusionguidelines.org.uk/ | title = Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee - Transfusion Guidelines | last = Target Information Systems Ltd|website=transfusionguidelines.org.uk|language=en|access-date=2021-04-01}}</ref>  
In the [[United States]] a temporary ban on donations from ME/CFS patients was put in place due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref name="PostRedCross2010" /><ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/ | title = XMRV testing in the UK | last = | first = | authorlink =  | date = 2010 | website = ME Association|language=en-US|archive-url=|archive-date=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name="PostRedCross2010">{{Cite news | url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html | title = Red Cross bars chronic fatigue patients from donating blood | last = Stein | first = Rob | authorlink = | date = Dec 3, 2010|publisher=Washington Post|archive-url=|archive-date=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name="Redaction2012">{{Cite journal | date = Dec 2012 | title = Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12 | pages = 799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name="TN2012">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/ | title = Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> Currently the US American Red Cross no longer have statements barring transfusions or transplants from ME/CFS patients, but patients are expected to be in "good health" which would exclude most.<ref name="RedCross">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|access-date=2019-02-13 | title = Frequently Asked Questions | date = | last = | first = | authorlink = |archive-url=|archive-date=|website=American Red Cross|quote=Your search for "Chronic fatigue syndrome" returned no results.}}</ref> Patient charities discouraged ME/CFS patients from donating blood,<ref name="MassBlood2015">{{Cite web |url=https://www.massmecfs.org/research/recent-research/19-xmrv/237-aabbs-recommendation-on-cfidsme-and-blood-donation | title = AABB's recommendation on ME/CFS and blood donation | date = Nov 25, 2015 |website=[[Massachusetts ME/CFS & FM Association]]}}</ref> but the American Association of Blood Banks advises to either accept or defer donors based on "clinical judgment of the donor's health status".<ref name="AABBOct2012">{{Cite web | last = American Association of Blood Banks | url=https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/xmrvfactsheet.pdf?sfvrsn=cd162fa3_2  | date = October 2012  | title = Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and other Polytropic Murine Leukemia Viruses (pMLV) |pages = 3 |quote=An updated AABB Association Bulletin #12-05 (November 2012) states that individual collectors of blood and cellular therapy products should accept or defer donors with a history of CFS based on their clinical judgment of the donor's health status.}}</ref>


==It is not tiredness==
[[New Zealand]] bans blood donation from anyone with ME/CFS.<ref name="NZBlood">{{Cite web |url = https://www.nzblood.co.nz/become-a-donor/am-i-eligible/detailed-eligibility-criteria/ | title = Detailed Eligibility Criteria|access-date=2022-05-25 | date = |website=NZ Blood|quote=People with a diagnosis of Chronic Fatigue Syndrome are permanently ineligible from donating blood in New Zealand}}</ref> [[Australia]] has a prohibition on blood donation as a precaution because it has not been established if ME/CFS could be caused by a transmissible infection.<ref name="AusBloodDonation">https://www.lifeblood.com.au/faq/eligibility/medical-conditions-and-procedures/chronic-fatigue-syndrome</ref>


=== Symptoms ===
== Mini-Docs ==
Symptom presentation varies enormously between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear. There are many symptoms which people with ME/CFS experience, though those listed below are arguably the most common:
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After physical or mental exertion (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program) there is a payback which can be delayed 24-48 hours and can last 24 hours or more. The patient will experience even greater fatigue as well as exasperate the flu-like symptoms and body pain. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref>[http://solvecfs.org/unraveling-post-exertional-malaise/ Unraveling Post-Exertional Malaise - Solve ME/CFS Initiative By: Jennifer M. Spotila, J.D. - Plus a link to all 4 parts]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref>  
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED
 
Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her illness, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0 | title = What happens when you have a disease doctors can't diagnose | date = Jan 17, 2017|access-date=|website=YouTube | last = Brea | first=Jennifer | authorlink=Jennifer Brea|archive-url=|archive-date=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose | title = What happens when you have a disease doctors can't diagnose | date = Jun 2016|access-date=|website=TED | last = Brea | first=Jennifer | authorlink=Jennifer Brea|archive-url=|archive-date=}}</ref>
 
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>
 
[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online
 
This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw | title = Invisible Illness - Stories of Chronic Fatigue Syndrome | date = Jul 10, 2015 |access-date=|website=YouTube | last = Weber | first = Veronica | authorlink=|archive-url=|archive-date=|publisher=Palo Alto Online}}</ref>


<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>


:Regarding PEM the [[CFIDS Association of America]] states: "This is a term which describes a symptom in which exercise or exertion can bring on malaise (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold)."<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html - What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref>
''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]


*[[Chronic fatigue]]
This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU | title = Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome | date = Oct 16, 2018|access-date=|website=YouTube | last = | first = | authorlink = David Kaufman|archive-url=|archive-date=|publisher=Unrest Film}}</ref>
*Chronic pain
*[[Cognitive dysfunction]]
*[[Unrefreshing sleep]], and sleep disturbance
*[[Orthostatic intolerance]], such as [[Postural orthostatic tachycardia syndrome]] ([[POTS]]) or [[Neurally mediated hypotension]] ([[NMH]])
*[[Neuroinflammation]]
*Neurological disturbances such as muscle spasms, numbness/tingling, sensory overload


===Biological abnormalities===
==Epidemiology ==
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. While it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the Central Nervous System, Autonomic Nervous System, Immune system, and energy metabolism.<ref name="IOM2015MECFS"/> Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a biomarker of the condition, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name="IOM2015-clinicians" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref name="epidemiology">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html | title = Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-11-08 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-01-29}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html | title = ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-01-29}}</ref><ref>{{Cite web|url=https://www.massmecfs.org/pediatric-me-cfs-home-page | title = Pediatric ME/CFS Home Page|website=massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal | last = Capelli | first = E. | last2 = Zola | first2 = R. | last3 = Lorusso | first3 = L. | last4 = Venturini | first4 = L. | last5 = Sardi | first5 = F. | last6 = Ricevuti | first6 = G. | date = Oct 2010 | title = Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|volume=23|issue=4 | pages = 981–989|doi=10.1177/039463201002300402|issn=0394-6320|pmid=21244747}}</ref> while the CDC states 4:1.<ref name="epidemiology" />
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html | title = Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2017-10-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref name="pediatric">{{Cite journal | last = | first = | date = 2015-03-16 | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome {{!}} Pediatric ME/CFS |url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume= | page = 181|pages = |doi=10.17226/19012|issue=|via=|quote=}}</ref> although it is usually diagnosed in adults. <ref name="what-is" /> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news | url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/ | title = ME/CFS in Children | first = David S. | last = Bell | authorlink =  David Bell | date = 2016-06-25 | website = [[Open Medicine Foundation]]|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html | title = Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-10-28}}</ref><ref name="pediatricprimer" /> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links | title = Pediatric ME/CFS links|website=[[Massachusetts ME/CFS & FM Association]]|language=en-GB|access-date=2018-08-11}}</ref><ref name="IOM2015-clinicians" /><ref name="Carruthers, 2003" /><ref name="ICC2011criteria" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/ | title = How Many People Have ME/CFS?|website=[[American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society]]|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref name="KeyFacts">{{Cite web|url=https://www.nap.edu/resource/19012/MECFS_KeyFacts.pdf | title = Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts | last = | first = | authorlink =  | date = 2015 | website = National Academies|archive-url=|archive-date=|access-date=}}</ref><ref>{{Cite book |url=https://www.nap.edu/read/19012/chapter/4 | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness | last = | first = |publisher=National Academies of Medicine|chapter =Chapter 4| year = 2015 |isbn=|editor-link=|location=|pages=32|language=en|quote=}}</ref> 90% of patients are undiagnosed.<ref name="what-is" />
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name="Cairns2005">{{Cite journal | last = Cairns | first = R. | last2 = Hotopf | first2 = M. | date = Jan 2005 | title = A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name="Cairns2005" /><ref>{{Cite journal | last= Joyce | first = J. | last2 = Hotopf | first2 = M. | last3 = Wessely | first3 = S. | date = Mar 1997 | title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review | url = https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>


*[[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014"/>, Younger's Leptin study <ref name="JohnsonC20150126younger"/>
==Evidence of a disease==
*Reduced brain white matter study by [[Stanford ME/CFS Initiative]]<ref name="StanfordMed20141028"/> New York Times Article with brain images.<ref name="TullerD20141124brain"/>Three major brain abnormalities.<ref>[http://privatehealthcarereports.com/chronic-fatigue-patients-suffer-3-major-brain-abnormalities-findings-may-lead-to-clearer-diagnosis/ Chronic Fatigue Patients Suffer 3 Major Brain Abnormalities; Findings May Lead To Clearer Diagnosis. - Private Health Care]</ref>
*Immune findings: [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune"/>
*[[Metabolic features of chronic fatigue syndrome]] by the Open Medicine Foundation show blood chemical signature.
*Autonomic nervous system:
*[[Natural killer cell]] findings
*Gut [[Dysbiosis]]
*[[Rituximab]]


===Epidemiology===
=== Symptoms ===
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web | title = Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=[[Centers for Disease Control and Prevention]] | date = 2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.


Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the condition used.<ref name="ICC2011criteria"/> In the US, estimates range between 836,000 and 2.5 million people with the condition, though true numbers are under-reported. It is estimated that 84-91% of people with the condition remain undiagnosed.<ref name="IOM2015MECFS"/>
[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|'''physical''' or '''mental''' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep]]; [[headache]]s and [[migraine]]s; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be [[Delayed onset of post-exertional symptoms|delayed 24-72 hours]] and depending on ME/CFS severity can last days, weeks, or even months]].<ref name="CDC-symptoms" />


*Level of disability (Norwegian study HRQoL)<ref name="Hvidberg2015"/> (suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)
[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her illness worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM"[[Canadian Consensus Criteria#Definition|option]]"]]


===Causes & triggers===
[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]
*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Herpesvirus]]es including [[Epstein-Barr virus]]<ref name="Hickie2006"/>, [[Q fever]]<ref name="Hickie2006"/>, Ross River Virus<ref name="Hickie2006"/>, ([[Ebola]]?)<ref name="Hickie2006"/>
*Non-viral triggers - [[trauma]], chemical


===Persistence hypotheses===
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840 | title = I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv | last = Croxall | first = Jack | date = 2019-01-17 | website = @JackCroxall|language=en|access-date=2019-01-17}}</ref>]]
*Immune findings


===Prognosis===
[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak, etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096 | title = First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak, etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF | last = Karen | date = 2019-01-17 | website = @hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]
Dr. [[David Bell]], who serves on the Scientific Advisory Board for the [[Open Medicine Foundation]], discusses three stages of the disease in the article [http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS].


==== Three stages ====
[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web | title = #TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p | url = https://twitter.com/Authorportrait/status/1085815918846832640 | website = @Authorportrait | date = 2019-01-17|access-date=2019-01-17|language=en | first = Henry | last = Köhler}}</ref>]]
*At the '''''first stage''''', there is an acute illness where [[EBV]] is likely responsible for most adolescents but there is no standard viral illness. The initial virus likely fades away in a week and the patient feels better and is ready for regular activities. He adds "in a person with a gradual onset of symptoms, this stage would be different."
*'''''Second stage''''' "occurs when the symptoms do not disappear, but persist for months to years in roughly the same severity. There is little variation day-to-day, and this time is very confusing. Many medical providers are contacted, most giving conflicting opinions varying from psychological disorders to possible exotic infections, but the tests come back normal."
*In the '''''third stage''''' patients will have mild, gradual improvements over years and patients adjust their lives to the symptoms. Patients may look well and recovery is thought to have taken place. Some patients will make a full recovery in 3-4 years but "recovery and improvement are completely different."<ref>[http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS – Open Medicine Foundation By: David S. Bell, MD]</ref>


Dr. Bell has great concern for patients 35 years old who had become ill as teens and has been studying a group that first became ill in 1985. "Some of the young adults rated their health as “good,” while the amount of activity they could perform was minimal. They had become so used to their performance level, they accepted it as their new normal. Unfortunately, many of them, while they described their health as good, they were unable to work full time or carry on other duties." It is now understood that persons with ME/CFS do not have a good long-term prognosis and it is actually poor as "full recovery from untreated CFS is rare."<ref>[http://www.openmedicinefoundation.org/2016/08/01/prognosis-of-mecfs/ Prognosis of ME/CFS – Open Medicine Foundation By: David S. Bell, MD]</ref>
*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After '''physical or mental''' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name="whatis" /><ref name=":0">{{Cite news | url=https://phoenixrising.me/archives/11883 | title = Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D. | last=Spotlia | first=Jenny | date = 2010-08-06|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html | title = International CFS/ME Awareness Day - 12th May 2019 | last = Hartley | first = Simon|website=whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal | last = Lindheimer | first=Jacob B. | last2 = Meyer | first2 = Jacob D. | last3 = Stegner | first3 = Aaron J. | last4 = Dougherty | first4 = Ryan J. | last5 = Van Riper | first5 = Stephanie M. | last6 = Shields | first6 = Morgan | last7 = Reisner | first7 = Amanda | last8 = Shukla | first8 = Sanjay K. | last9 = Light | first9 = Alan R. | date = 2017-04-03 | title = Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=5|issue=2 | pages = 69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal | last = Yoshiuchi | first = Kazuhiro | last2 = Cook | first2 = Dane B. | last3 = Ohashi | first3 = Kyoko | last4 = Kumano | first4 = Hiroaki | last5 = Kuboki | first5 = Tomifusa | last6 = Yamamoto | first6 = Yoshiharu | last7 = Natelson | first7 = Benjamin H. | date = 2007-12-05 | title = A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5 | pages = 963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name="VanNess2010">{{Cite journal | last = VanNess | first = J. Mark | last2 = Stevens | first2 = Staci R. | last3 = Bateman | first3 = Lucinda | last4 = Stiles | first4 = Travis L. | last5 = Snell | first5 = Christopher R. | date = Feb 2010 | title = Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration's (FDA) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name="whatis" /><ref name=":0" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]
*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[Unrefreshing sleep|unrefreshing]] sleep See also: [[sleep disturbance]] <ref name="DiagnosticAlgorithm" /><ref name="IOM2015-clinicians" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*<span class="plainlinks">[[:Category:Neurological signs and symptoms|neurological signs and symptoms]]</span> See also: [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]


'''Few Return to Pre-illness State of Functioning'''
=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>


In about 40% of people with ME/CFS, the condition will improve over time, though recovery rates from the condition are generally quite low (less than 10%). The condition may also take a relapsing/remitting course, so individuals who appear to have recovered, may actually be in remission. For 5-20% of people, the condition is degenerative. Some studies suggest that prognosis is better for those with less severe symptoms, and who developed the condition at a younger age (childhood-young adulthood), though these findings are not consistent. It is clear that few people will return to their pre-illness state of health and functioning.<ref name="CairnsR2005prog"/><ref name="JoyceJ1997prog"/><ref name="Johnson20130706"/>
=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[https://www.nap.edu/resource/19012/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Primary Symptoms]


===Treatments===
'''Canada guides on symptoms'''
There are currently no [[FDA]] approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer"/> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]


Two treatments that have garnered much attention are [[Ampligen]] and [[Rituximab]]. Many people have reported enormous benefit from Ampligen, some doctors have been prescribing it for ME/CFS for decades. Attempts to obtain FDA approval for Ampligen in the US have failed so, despite its usefulness, it is unavailable to many. Rituximab, a lymphoma drug, has shown promising results in initial trials in Norway, and there are groups crowdsourcing funding for further trials in other countries. [[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[Low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref> http://www.psy.uab.edu/younger/research.html</ref>
===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no [[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis|medical abnormalities]] found in people with the disease. As a result, ME/CFS symptoms are often considered to be [[Medically unexplained physical symptoms|medically unexplained]], and therefore [[Psychologization|psychological]] in origin. While it is true that the disease is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the [[central nervous system]], [[autonomic nervous system]], [[immune system]], and [[Metabolic|energy metabolism]].<ref name="IOM2015MECFS">{{Cite book | last1 = Institute of Medicine (US)| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| publisher = The National Academies Press | location = Washington, DC, US| date = February 10, 2015 | isbn = 978-0-309-31689-7| url = https://pubmed.ncbi.nlm.nih.gov/25695122/ }}</ref> Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a [[Diagnostic biomarker|biomarker]] of the illness, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the illness, it cannot yet be determined whether these are a cause or consequence of the illness.
* [[Gastrointestinal system]]
* [[Natural killer cell]] findings


===Exercise as treatment===
==== Notable studies ====
* [[Cytokine#Notable_studies|Cytokine ("Notable studies")]]
*Immune findings by [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune">{{Cite journal | last1 = Hornig | first1 = Mady | authorlink1 = Mady Hornig | last2 = Montoya | first2 = José G | authorlink2 = Jose Montoya | last3 = Klimas | first3 = Nancy G | authorlink3 = Nancy Klimas | last4 = Levine | first4 = Susan | authorlink4 = Susan Levine | last5 = Felsenstein | first5 = Donna | authorlink5 = Donna Felsenstein | last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman | last7 = Peterson | first7 = Daniel L | authorlink7 = Daniel Peterson | last8 = Gottschalk | first8 = C Gunnar | authorlink8 = Gunnar Gottschalk | last9 = Schultz | first9 = Andrew F | authorlink9 = Andrew Schultz | last10 = Che | first10 = Xiaoyu | authorlink10 = Xiaoyu Che | last11 = Eddy | first11 =  Meredith L | authorlink11 = Meredith Eddy | last12 = Komaroff | first12 = Anthony L | authorlink12 = Anthony Komaroff | last13 = Lipkin | first13 = W Ian | authorlink13 = Ian Lipkin | title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness | journal = Science Advances | volume = 1 | issue = 1 | date = February 1, 2015 | url = http://advances.sciencemag.org/content/1/1/e1400121 }}</ref>
*[[List of enterovirus infection studies]]


Two common treatment recommendations for ME/CFS are [[Graded Exercise Therapy]] ([[GET]]) and [[Cognitive behavioral therapy]] ([[CBT]]). These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey"/> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012"/>
*2014, [[Neuroinflammation]] Japanese Neuroinflammation study,<ref name="NakatomiY2014">{{Cite journal | last1 = Nakatomi | first1 = Yasuhito | authorlink1 = Yasuhito Nakatomi | last2 = Mizuno | first2 = Kei | authorlink2 = Kei Mizuno | last3 = Ishii | first3 = Ishii | authorlink3 = Akira Ishii | last4 = Yasuhiro | first4 = Wada | authorlink4 = Yasuhiro Wada | last5 = Masaaki | first5 = Tanaka | authorlink5 = Masaaki Tanaka | last6 = Shusaku | first6 = Tazawa | authorlink6 = Shusaku Tazawa | last7 = Kayo | first7 = Onoe | authorlink7 = Kayo Onoe | last8 = Sanae | first8 = Fukuda | authorlink8 = Sanae Fukuda | last9 = Joji | first9 = Kawabe | authorlink9 = Joji Kawabe | last10 = Kazuhiro | first10 = Takahashi | authorlink10 = Kazuhiro Takahashi | last11 = Yosky | first11 =  Kataoka | authorlink11 = Yosky Kataoka | last12 = Susumu | first12 = Shiomi | authorlink12 = Susumu Shiomi | last13 = Kouzi | first13 = Yamaguti | authorlink13 = Kouzi Yamaguti | last14 = Masaaki | first14 =  Inaba | authorlink14 = Masaaki Inaba | last15 = Hirohiko | first15 =  Kuratsune | authorlink15 = Hirohiko Kuratsune | last16 = Yasuyoshi | first16 = Watanabe | authorlink16 = Yasuyoshi Watanabe | title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study | journal = Journal of Nuclear Medicine | volume = 55|issue =6 | page = 945-50 | date = Mar 24, 2014 | pmid = 24665088 | doi = 10.2967/jnumed.113.131045| url = http://jnm.snmjournals.org/content/55/6/945.long}}</ref> Younger's Leptin study<ref name="stanfordleptin" />
* 2014, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome<ref name="Zeineh2014">{{Cite journal | last = Zeineh | first = Michael M. | author-link = Michael Zeineh | last2 = Kang | first2 = James | authorlink2 = | last3 = Atlas | first3 = Scott W. | authorlink3 = | last4 = Raman | first4 = Mira M. | authorlink4 = | last5 = Reiss | first5 = Allan L. | authorlink5 = | last6 = Norris | first6 = Jane L. | authorlink6 = | last7 = Valencia | first7 = Ian | authorlink7 = Ian Valencia | last8 = Montoya | first8 = Jose G. | authorlink8 = Jose Montoya | date = Feb 2015 | title = Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|url=http://pubs.rsna.org/doi/10.1148/radiol.14141079|journal=Radiology|language=en|volume=274|issue=2 | pages = 517–526|doi=10.1148/radiol.14141079|issn=0033-8419|pmc=|pmid=|access-date=|quote=|via=}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]
*2015, Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: Evidence of inflammatory pathology<ref name="stanfordleptin">{{Cite journal | last1 = Stringer | first1 = EA | last2 = Baker | first2 = KS | last3 = Carrol | first3 = IR | last4 = Montoya | first4 = JG | authorlink4 = Jose Montoya | last5 = Chu | first5 = L | authorlink5 = Lily Chu | last6 = Maeker | first6 = HT | last7 = Younger | first7 = JW | authorlink7 = Jarred Younger| title = Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: Evidence of inflammatory pathology | journal = J Transl Med.| date = Apr 9, 2013 | pmid = 23570606 | pmc = 3637529 | doi = 10.1186/1479-5876-11-93| url = http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-93 }}</ref> - [https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-93 (Full text)]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''


The [[PACE trial]], published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref> http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext</ref> The study was the subject of a series of investigative pieces by journalist [[David Tuller]] in late 2015, that were highly critical of the trial.<ref name="viroblogMECFS"/> A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition"/> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2"/> were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr"/> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the [[PACE trial]] continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.
*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU | title = ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study | date = 2018-12-14|access-date=|website=YouTube | last = Younger | first=Jarred | authorlink=Jarred Younger|archive-url=|archive-date=|publisher=SolveCFS}}</ref> (TALK)


One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of Post-Exertional Malaise (PEM), which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to [[deconditioning]].<ref name="TwiskF2015"/><ref> reference needed - Workwell Foundation studies</ref><ref> reference needed - the Lights epigenetic changes post-exercise</ref>
===Causes & triggers===
*Outbreaks - see [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Herpesvirus]]es including [[Epstein-Barr virus]]<ref name="Hickie2006">{{Cite journal | last1 = Hickie | first1 = Ian | authorlink1 = Ian Hickie | last2 = Davenport | first2 = Tracey | authorlink2 = Tracey Davenport | last3 = Wakefield | first3 = Denis | authorlink3 = Denis Wakefield | last4 = Vollmer-Conna | first4 = Ute | authorlink4 = Ute Vollmer-Conna | last5 = Cameron | first5 = Barbara | authorlink5 = Barbara Cameron | last6 = Vernon | first6 = Suzanne D | authorlink6 = Suzanne Vernon | last7 = Reeves | first7 = William C | authorlink7 = William Reeves | last8 = Lloyd | first8 = Andrew | authorlink8 = Andrew Lloyd | last9 = Dubbo Infection Outcomes Study Group| title = Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study| journal = BMJ | volume = 333| issue=575 | date = Sep 14, 2006 | pmid = 16950834 | doi = 10.1136/bmj.38933.585764.AE| url = http://www.bmj.com/content/333/7568/575.long }}</ref> [[Q fever]]<ref name="Hickie2006" />, [[Ross River virus]],<ref name="Hickie2006" /> potentially [[Ebola]],<ref name="Hickie2006" />
*Non-viral triggers - physical or psychological [[trauma]], chemical exposure


People with ME/CFS should approach exercise with caution, as there is much potential for harm.  
===Epidemiology===
Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the illness used.<ref name="ICC2011criteria" /> In the US, estimates range between 836,000 and 2.5 million people with the illness, though true numbers are under-reported. It is estimated that 84-91% of people with the illness remain undiagnosed.<ref name="IOM2015MECFS" />


Anaerobic threshold, use of HR monitors for activity and pacing. Analeptic, not aerobic.  
*Level of disability (eg, Norwegian study HRQoL by Hvidberg, 2015) suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)<ref name="Hvidberg2015">{{Cite journal | last1 = Hvidberg | first1 = Michael Falk | authorlink1 = Michael Falk Hvidberg | last2 = Brinth | first2 = Louise Schouborg | authorlink2 = Louise Schouborg Brinth | last3 = Olesen | first3 = Anne V | authorlink3 = Anne V Oleson | last4 = Petersen | first4 = Karin D | authorlink4 = Karin Peterson | last5 = Ehlers | first5 = Lars | authorlink5 = Lars Ehlers | title = The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)| journal = PLoS One | date = Jul 6, 2015 | doi = 10.1371/journal.pone.0132421| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132421}}</ref>
Energy envelope/pacing - people do better if stay within their envelope than to push to increase activity


===Severely ill patients===
===Severely ill patients===
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):
Considerable variation exists in the severity of the illness. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):


*Mild = 50% reduction in pre-illness activity levels
*Mild = 50% reduction in pre-illness activity levels
Line 96: Line 156:
*Very Severe = totally bedridden, and needing help with basic functions.  
*Very Severe = totally bedridden, and needing help with basic functions.  


At least 25% of people with ME/CFS are bedbound or housebound, often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS"/> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [http://www.openmedicinefoundation.org/mecfs-severely-ill-big-data-study/ Severely Ill Big Data Study] will be the first in-depth study of people with a severe form of ME/CFS.  
At least [[Severe and very severe ME|25% of people with ME/CFS are bed-bound or housebound]], often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS" /> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [[ME/CFS Severely Ill, Big Data Study]] will be the first in-depth study of people with a severe form of ME/CFS.
 
Notable patients with severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]] (had been sanctioned), [[Laura Hillenbrand]], [[Tom Kindlon]], [[Doctor Speedy]], [[Naomi Whittingham]], [[Jennifer Brea|Jen Brea]], and [[Emma Shorter]].  


Notable patients with severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]], [[Lynn Gilderdale]], [[Laura Hillenbrand]], [[Tom Kindlon]], [[Vanessa Li]], [[Doctor Speedy]], [[Naomi Whittingham]].
Though uncommon, there have been [[Causes of death|instances of deaths which have been attributed to the disease]]. (See: [[Sophia Mirza]] and [[Merryn Crofts]].) Also, see [[Vanessa Li]] and [[Lynn Gilderdale]].


Though uncommon, there have been instances of deaths which have been attributed to the condition (see [[Sophia Mirza]]).
===Centers for Disease Control and Prevention (CDC) ===
*Jul 3, 2017, the [[Centers for Disease Control and Prevention|CDC]]'s Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) recommendations have been removed.<ref>{{Cite web|url=http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ | title = Trial By Error: The CDC Drops CBT/GET | last = Tuller | first=David | date = 2017-07-10 | website = [[Virology blog]]|language=en-US|archive-url=|archive-date=|access-date=2018-08-23}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/index.html | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | date = 2018-07-03 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-08-23}}</ref>


== Notable studies ==
*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC.gov]</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html | title = New ME/CFS Web Content for Healthcare Providers {{!}} CDC Online Newsroom {{!}} CDC | date = 2018-07-12 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-08-23}}</ref>
*[[Pathways to prevention report]] (P2P)
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web | title = Chronic Fatigue Syndrome: It's Real, and We Can Do Better |url = https://www.medscape.com/viewarticle/908622?src=rss| website = Medscape |access-date=2019-02-25 | date = Feb 25, 2019 | last = Unger | first=Elizabeth | authorlink = Elizabeth Unger|archive-url=|archive-date= | last2 = Medscape}}</ref>
*[[Institute of Medicine report]]  
 
*[[PACE trial]] is a highly criticized UK trial designed by psychiatrists to promote [[GET]] and [[CBT]] as therapy which is deemed harmful and useless for ME/CFS patients by many clinicians, researchers, patients, and advocates.
'''MEAction input'''
*[[Metabolic features of chronic fatigue syndrome]]
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] [[The MEAction Network]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's [[ME/CFS]] page have been created from patient feedback on the updates as well as asking for further patient input.
*[[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)]]


==History==
== Tests ==
*[[Osler's Web]] is a book on the early history of CFS.
* [[Natural killer cell]] (NKC) Blood Test
*[[Thirty Years of Disdain]] picks up on the ME/CFS history where Osler's Web leaves off.
*[[List of news articles on ME and CFS]]
*[[Sophia Mirza]]'s life ended due to CFS.
*[http://me-pedia.org/wiki/Disabled_in_Tory_Britain#PACE_trial UK agencies involved in the implementation of the PACE trial. Disabled in Tory Britain - PACE trial]


==Learn more==
* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?] By the [[Open Medicine Foundation]]
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].
*[[Systemic Exertion Intolerance Disease]] (SEID) [http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf ME/CFS Clinicians Guide]
*[http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf IACFS/ME Primer for Clinical Practitioners - 2014 Edition]<ref name="IACFSME2014primer"/>
*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf Myalgic Encephalomyelitis - Adult & Pediatric - International Consensus Criteria Primer for Medical Practitioners]<ref name="ICP2011primer"/>
*[http://www.meassociation.org.uk/2014/07/our-purple-booklet-clear-clinical-guidance-and-the-latest-research-all-wrapped-up-in-52-pages/ ME Association clinical guidance]<ref name="MEASSUKprimer2013"/>
*[http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf ME/CFS Treatment Resource Guide for Practitioners by A Martin Lerner, MD]<ref name="LernerPrimer2011"/>
*[http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598 The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem], 2016.<ref name="Edwards2016"/>
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]] (CDC Video, 2016)
*[[Notable studies]]


==See also==
==Treatments==
*[https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose#t-826118 What happens when you have a disease doctors can't diagnose] TED Talk by [[Jennifer Brea]]
There are currently no [[FDA]] approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer">{{Cite web | last1 = International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (IACFS/ME) | last2 = Friedberg | first2 = Fred | authorlink2 = Fred Friedberg | last3 = Bateman | first3 = Lucinda | authorlink3 = Lucinda Bateman | last4 = Bested | first4 = Alison C | authorlink4 = Alison Bested | last5 = Davenport | first5 = Todd | authorlink5 = Todd Davenport | last6 = Friedman | first6 = Kenneth J | authorlink6 = Kenneth Friedman | last7 = Gurwitt | first7 = Alan R | authorlink7 = Alan Gurwitt | last8 = Jason | first8 = Leonard A | authorlink8 = Leonard Jason | last9 = Lapp | first9 = Charles W | authorlink9 = Charles Lapp | last10 = Stevens | first10 = Staci R | authorlink10 = Staci Stevens | last11 = Underhill | first11 =  Rosemary A | authorlink11 = Rosemary Underhill | last12 = Vallings | first12 = Rosamund | authorlink12 = Rosamund Vallings | title = 2014 Primer for Clinical Practitioners (CFS/ME) | journal = IACFS/ME| date = Jul 2014| url = https://www.massmecfs.org/images/pdf/Primer_2014.pdf }}</ref> There are many [[:Category:Potential_treatments|potential treatments]], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.  
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]
*[[Primer for patients]]
*[[Forgotten Plague]] Documentary
*[[Fibromyalgia]]
*[[David Tuller]] writes and speaks at length and in detail about the PACE Trial.


==References==
=== Drugs ===
<references>
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[AIM ImmunoTech]], and [[Rituximab]]. Many people have reported benefit from Ampligen;<ref name="TownCFS">{{Cite web|url=https://www.newyorker.com/culture/personal-history/a-town-for-people-with-chronic-fatigue  | title = A Town for People with Chronic-Fatigue Syndrome|website=New Yorker | date = Sep 3, 2019 | first = Mike | last = Mariani|access-date=2022-04-13}}</ref>


<!-- ....1....+....2....+....3....+....4....+....5....+....6....+....7....+....8....+....9....+....0 --->
Attempts to obtain FDA approval for Ampligen in the [[United States]] have failed so it is unavailable to many.<ref name="experimental">{{Cite web|url=https://ammes.org/experimental-treatments/ | title = Experimental treatments | last = | first = | date = |website=[[American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society]]|language=en-US|archive-url=|archive-date=|access-date=2021-03-18}}</ref> [[Argentina]] approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news | url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html | title = Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic | last = Hemispherx Biopharma Inc | first = | date = Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|language=en-US}}</ref><ref>{{Cite news | url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf | title = Hemispherx Biopharma, Inc. Executive Informational Overview | last = | first = | date = Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html | title = Hemispherx ships Ampligen for European chronic fatigue syndrome program | last = George | first = John | date = Jul 25, 2016 | website = bizjournals.com|archive-url=|archive-date=|access-date=2018-08-13}}</ref> In July of 2018, AIM ImmunoTech announced the expansion of its [[compassionate use|Treatment Protocol/Expanded Access Programs]] (compassionate use) for ME/CFS in the United States, known as '''AMP-511''', to new patients.<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html | title = Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | last = | first = | authorlink =  | date = Jan 2, 2019 | website = finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|access-date=2019-02-10}}</ref> The most recent Ampligen trial was published in 2020.<ref name="Strayer2020">{{Cite journal | title = Effect of disease duration in a randomized Phase III trial of rintatolimod, an immune modulator for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2020-10-29|url=https://dx.plos.org/10.1371/journal.pone.0240403|journal=PLOS ONE|volume=15|issue=10| pages = e0240403 | last = Strayer | first=David R. | author-link = David Strayer | last2 = Young | first2 = Diane | author-link2 = | last3 = Mitchell | first3 = William M. | authorlink3 = William Mitchell|language=en|doi=10.1371/journal.pone.0240403|pmc=PMC7595369|pmid=33119613|access-date=|issn=1932-6203|quote=|via=}}</ref>


<ref name="Edwards2016">{{Citation
[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,<ref name="FlugeMain2015">{{Cite journal | last = Fluge | first = Øystein | authorlink = Øystein Fluge | last2 = Risa | first2 = Kristin | authorlink2 = | last3 = Lunde | first3 = Sigrid | author-link3 = | last4 = Alme | first4 = Kine | author-link4 = | last5 = Rekeland | first5 = Ingrid Gurvin | authorlink5 = | last6 = Sapkota | first6 = Dipak  | authorlink6 = | last7 = Kristoffersen | first7 = Einar Kleboe | last8 = Sørland | first8 = Kari | last9 = Bruland | first9 = Ove | date = 2015-07-01 | editor-last = van der Feltz-Cornelis|editor-first = Christina | title = B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment|url=http://dx.plos.org/10.1371/journal.pone.0129898|journal=PLOS ONE|language=en|volume=10|issue=7| pages = e0129898|doi=10.1371/journal.pone.0129898|issn=1932-6203|pmc=4488509|pmid=26132314|access-date=|quote=|via=}}</ref> and there were groups crowdsourcing funding for further trials in other countries. In 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab.<ref>{{Cite web|url=http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/ | title = Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails | date = 2017-11-26 | website = Simmaron Research|language=en-US|access-date=2019-04-23}}</ref> A phase III trial published in 2019 showed Rituximab did not improve ME/CFS.<ref name="phase3-2019">{{Cite journal | last = Fluge | first = Øystein | last2 = Rekeland | first2 = Ingrid G. | last3 = Lien | first3 = Katarina | last4 = Thürmer | first4 = Hanne | last5 = Borchgrevink | first5 = Petter C. | last6 = Schäfer | first6 = Christoph | last7 = Sørland | first7 = Kari | last8 = Aßmus | first8 = Jörg | last9 = Ktoridou-Valen | first9 = Irini | date = 2019-04-02 | title = B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial|url=https://www.ncbi.nlm.nih.gov/pubmed/30934066|journal=Annals of Internal Medicine|doi=10.7326/M18-1451|issn=1539-3704|pmid=30934066}}</ref>
| last1 = Edwards | first1 = JCW | authorlink1 = Jonathan Edwards
| last2 = McGrath | first2 = S | authorlink2 = Simon McGrath
| last3 = Baldwin | first3 = A | authorlink3 = Adrian Baldwin
| last4 = Livingstone | first4 = M | authorlink4 = Mark Livingstone
| last5 = Kewley | first5 = A | authorlink5 = Andrew Kewley
| title = The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 4 | issue = 2 | pages = 63–69
| date = 2016-04-02
| doi = 10.1080/21641846.2016.1160598
| url = http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598
}}</ref>


<ref name="ICP2011primer">{{citation
[[Jarred Younger]] announced he will be undertaking a trial of [[low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref>{{Cite web|url=https://www.youtube.com/watch?v=95OlnK-FEdk | title = 2017 Study -- Low Dose Naltrexone for Chronic Fatigue Syndrome | last = Younger | first=Jarred | date = 2016-12-12 | website = YouTube|publisher=Younger Lab|archive-url=|archive-date=|access-date=}}</ref>
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Bell | first12= DS | authorlink12= David Bell
| last13 = Carlo-Stella | first13= N | authorlink13= Nicoletta Carlo-Stella
| last14 = Chia | first14= J | authorlink14= John Chia
| last15 = Darragh | first15= A | authorlink15= Austin Darragh
| last16 = Gerken | first16= A | authorlink16= Anne Gerken
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Light | first20= KC | authorlink20= Kathleen Light
| last21 = Marshall-Gradisnik | first21= S | authorlink21= Sonya Marshall-Gradisnik
| last22 = McLaren-Howard | first22= J | authorlink22= John McLaren-Howard
| last23 = Mena | first23= I | authorlink23= Ismael Mena
| last24 = Miwa | first24= K | authorlink24= Kunihisa Miwa
| last25 = Murovska | first25= M | authorlink25= Modra Murovska
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners
| date = 2012
| isbn = 978-0-9739335-3-6
| url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf
}}</ref>


<ref name="IACFSME2014primer">{{citation
=== Treating other conditions ===
| last1 = International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (IACFS/ME)
Different forms of [[Orthostatic intolerance|OI]] are treated with beta-blockers (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref name="ICP2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 =  J | authorlink14 = John Chia | last15 = Darragh | first15 =  A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 =  D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25 = Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbidities or overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web | title = Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=[[Centers for Disease Control and Prevention]] | date = 2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI.<ref name=":05" /><ref name="Carruthers, 2003" />
| last2 = Friedberg | first2 = Fred | authorlink2 = Fred Friedberg
| last3 = Bateman | first3 = Lucinda | authorlink3 = Lucinda Bateman
| last4 = Bested | first4 = Alison C | authorlink4 = Alison Bested
| last5 = Davenport | first5 = Todd | authorlink5 = Todd Davenport
| last6 = Friedman | first6 = Kenneth J | authorlink6 = Kenneth Friedman
| last7 = Gurwitt | first7 = Alan R | authorlink7 = Alan Gurwitt
| last8 = Jason | first8 = Leonard A | authorlink8 = Leonard Jason
| last9 = Lapp | first9 = Charles W | authorlink9 = Charles Lapp
| last10 = Stevens | first10= Staci R | authorlink10= Staci Stevens
| last11 = Underhill | first11= Rosemary A | authorlink11= Rosemary Underhill
| last12 = Vallings | first12= Rosamund | authorlink12= Rosamund Vallings
| title = 2014 Primer for Clinical Practitioners (CFS/ME)
| journal = IACFS/ME
| date = Jul 2014
| url = http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf
}}</ref>


<ref name="LernerPrimer2011">{{citation
===Exercise as treatment===
| last1 = Lerner | first1 = AM | authorlink1 = A Martin Lerner
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was studying at Harvard; while on a trip to [[Kenya]] she became very ill with what would eventually be diagnosed as [[ME/CFS]]. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen then needed to use a wheelchair,]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
| title = ME/CFS Treatment Resource Guide for Practitioners
Two common treatment recommendations for ME/CFS are [[GET]] and [[CBT]]. These treatments are based on the disproven hypothesis that the illness might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and [[illness beliefs|fear and avoidance of activity]]. GET and CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that are claimed to result in avoidance of activity, and by increasing fitness through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which provides evidence that exercise is harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey">{{Cite web | last1 = ME Association (UK) | authorlink1 = ME Association | date = May 29, 2015 | title = Our CBT, GET and Pacing Report calls for major changes to therapies offered for ME/CFS| url = http://www.meassociation.org.uk/2015/05/23959/ }}</ref> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012">{{citation | title = Norwegian patient survey: Experiences of therapeutic approaches (2012) | journal = Phoenix Rising Forum | date = Feb 22, 2016| url = http://forums.phoenixrising.me/index.php?threads/norwegian-patient-survey-experiences-of-therapeutic-approaches-2012-update.43193/ }}</ref>
| date = 2011
| url = http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf
}}</ref>


<ref name="MEASSUKprimer2013">{{citation
The [[PACE trial]], published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref name="Coyne2016">{{Cite journal | last = Coyne | first = James Charles | last2 = Laws | first2 = Keith R | date = 2016 | title=Results of the PACE follow-up study are uninterpretable|url=http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext|journal=The Lancet Psychiatry|language=English|volume=3|issue=2| pages = e6–e7|doi=10.1016/S2215-0366(15)00551-9|issn=2215-0366|via=}}</ref> The study was the subject of a series of investigative pieces by journalist [[David Tuller]] in late 2015, that were highly critical of the trial.<ref name="viroblogMECFS" /> A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition">{{Cite web | last1 = #MEAction | authorlink1 = #MEAction| title = Petition: Misleading Claims Should Be Retracted
| last1 = Shepherd | first1 = C | authorlink1 = Charles Shepherd
| publisher = #MEAction | date = Oct 2015 | url = http://my.meaction.net/petitions/pace-trial-needs-review-now}}</ref> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2">{{Cite web | last1 = Davis | first1 = Ronald W | authorlink1 = Ronald Davis | last2 = Edwards | first2 = Jonathan C W | authorlink2 = Jonathan Edwards | last3 = Jason | first3 = Leonard A | authorlink3 = Leonard Jason | last4 = Levin | first4 = Bruce | authorlink4 = Bruce Levin | last5 = Racaniello | first5 = Vincent R | authorlink5 = Vincent Racaniello | last6 = Reingold | first6 = Arthur L | authorlink6 = Arthur Reingold | last7 = Ablashi | first7 = Dharam V | authorlink7 = Dharam Ablashi | last8 = Baraniuk | first8 = James N | authorlink8 = James Baraniuk | last9 = Barcellos | first9 = Lisa F | authorlink9 = Lisa Barcellos | last10 = Bateman | first10 = Lucinda | authorlink10 = Lucinda Bateman | last11 = Bell | first11 = David S | authorlink11 = David Bell | last12 = Bested | first12 = Alison C | authorlink12 = Alison Bested | last13 = Broderick | first13 = Gordon | authorlink13 = Gordon Broderick | last14 = Chia | first14 = John | authorlink14 = John Chia | last15 = Chu | first15 = Lily | authorlink15 = Lily Chu | last16 = Enlander | first16 = Derek | authorlink16 = Derek Enlander | last17 = Fletcher | first17 = Mary Ann | authorlink17 = Mary Ann Fletcher | last18 = Friedman | first18 = Kenneth | authorlink18 = Kenneth Friedman | last19 = Kaufman | first19 = David L | authorlink19 = David Kaufman | last20 = Klimas | first20 = Nancy | authorlink20 = Nancy Klimas | last21 = Lapp | first21 = Charles W | authorlink21 = Charles Lapp | last22 = Levine | first22 = Susan | authorlink22 = Susan Levine | last23 = Light | first23 = Alan R | authorlink23 = Alan Light | last24 = Marshall-Gradisnik | first24 = Sonya | authorlink24 = Sonya Marshall-Gradisnik | last25 = Medveczky | first25 = Peter G | authorlink25 = Peter Medveczky | last26 = Nahle | first26 = Zaher | authorlink26 = Zaher Nahle | last27 = Oleske | first27 = James M | authorlink27 = James Oleske | last28 = Podell | first28 = Richard N | authorlink28 = Richard Podell | last29 = Shepherd | first29 = Charles | authorlink29 = Charles Shepherd | last30 = Snell | first30 = Christopher R | authorlink30 = Christopher Snell | last31 = Speight | first31 = Nigel | authorlink31 = Nigel Speight | last32 = Staines | first32 = Donald | authorlink32 = Donald Staines | last33 = Stark | first33 = Philip B | authorlink33 = Philip Stark | last34 = Stein | first34 = Eleanor | authorlink34 = Eleanor Stein | last35 = Swartzberg | first35 = John | authorlink35 = John Swartzberg | last36 = Tompkins | first36 = Ronald G | authorlink36 = Ronald Tompkins | last37 = Underhill | first37 = Rosemary | authorlink37 = Rosemary Underhill | last38 = Vallings | first38 = Rosamund | authorlink38 = Rosamund Vallings | last39 = VanElzakker | first39 = Michael | authorlink39 = Michael VanElzakker | last40 = Weir | first40 = William | authorlink40 = William Weir | last41 = Zinn | first41 = Marcie L | authorlink41 = Marcie Zinn | last42 = Zinn | first42 = Mark A | authorlink42 = Mark Zinn | title = An open letter to the Lancet - again | date = Feb 10, 2016| website = [[Virology blog]]| url = http://www.virology.ws/2016/02/10/another-request-for-data-from-the-pace-trial/}}</ref> were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr">{{Cite web | last1 = #MEAction | authorlink1 = #MEAction | title = 24 organisations in 14 countries tell QMUL: Release the PACE data | date = Mar 13, 2016| url = http://www.meaction.net/2016/03/13/24-organisations-in-14-countries-tell-qmul-release-pace-data/#comment-2518 }}</ref> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.
| last2 = Chaudhuri | first2 = A | authorlink2 = Abhijit Chaudhuri
| title = ME/CFS/PVFS An Exploration of the Key Clinical Issues ('Purple Booklet')
| date = 2013
| url = http://www.meassociation.org.uk/wp-content/uploads/2011/01/pruple-booklet-front-cover.jpg
}}</ref>


One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of [[post-exertional malaise]] (PEM), which is an exacerbation of symptoms following physical, mental or even emotional [[exertion]]. Studies have revealed immunological, muscular, [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]] and [[Cardiovascular system|cardiovascular]] abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary people, the adverse effects of exercise cannot be said to be due to deconditioning.<ref name="TwiskF2015">{{Cite journal | last1 = Twisk | first1 = Frank NM | authorlink1 = Frank Twisk | last2 = Geraghty | first2 = Keith J | authorlink2 = Keith Geraghty | title = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome | journal = Jacobs Journal of Physiology | volume = 1|issue =2|page =007 | date = Jul 11, 2015 | url = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf }}</ref>{{citation needed|reason=Workwell Foundation studies need to be cited here.}}{{citation needed|reason=The Lights epigenetic changes post-exercise study needs to be cited here.}}


<ref name="CairnsR2005prog">{{citation
People with ME/CFS should approach exercise with caution, as there is much potential for harm.  
| last1 = Cairns | first1 = R | authorlink1 = Ruth Cairns
| last2 = Hotopf | first2 = M | authorlink2 = Matthew Hotopf
| title = A systematic review describing the prognosis of chronic fatigue syndrome
| journal = Occupational Medicine | volume = 2005;55 | page = 20–31
| doi = 10.1093/occmed/kqi013
| url = http://occmed.oxfordjournals.org/content/55/1/20.full.pdf
}}</ref>


<ref name="JohnsonC20150126younger">{{citation
[[Anaerobic]] threshold, use of heart rate monitors for activity and pacing. Analeptic, not aerobic.
| last1 = Johnson | first1 = Cort | authorlink1 = Cort Johnson
[[Energy Envelope Theory|Energy envelope]]/[[pacing]] - people do better if stay within their envelope than to push to increase activity
| title = Getting “Younger”: Leptin, Chronic Fatigue Syndrome and Fibromyalgia]
| date = 26 Jan 2015
| url = http://www.cortjohnson.org/blog/2015/01/26/getting-younger-leptin-chronic-fatigue-fibromyalgia/
}}</ref>


<ref name="Hickie2006">{{citation
===Graded exercise therapy & Cognitive behavioral therapy ===
| last1 = Hickie | first1 = Ian | authorlink1 = Ian Hickie
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
| last2 = Davenport | first2 = Tracey | authorlink2 = Tracey Davenport
| last3 = Wakefield | first3 = Denis | authorlink3 = Denis Wakefield
| last4 = Vollmer-Conna | first4 = Ute | authorlink4 = Ute Vollmer-Conna
| last5 = Cameron | first5 = Barbara | authorlink5 = Barbara Cameron
| last6 = Vernon | first6 = Suzanne D | authorlink6 = Suzanne Vernon
| last7 = Reeves | first7 = William C | authorlink7 = William Reeves
| last8 = Lloyd | first8 = Andrew | authorlink8 = Andrew Lloyd
| last9 = Dubbo Infection Outcomes Study Group
| title = Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study
| journal = BMJ | volume = 2006; 333:575
| date = 14 Sep 2006
| pmid = 16950834 | doi = 10.1136/bmj.38933.585764.AE
| url = http://www.bmj.com/content/333/7568/575.long
}}</ref>


<ref name="Hornig20150201immune">{{citation
[[Graded exercise therapy|GET]] and [[Cognitive behavioral therapy|CBT]] are usually employed in the [[United Kingdom|UK]], [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the disproven [[biopsychosocial model]] of ME/CFS, backed up by the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.
| last1 = Hornig | first1 = Mady | authorlink1 = Mady Hornig
| last2 = Montoya | first2 = José G | authorlink2 = Jose Montoya
| last3 = Klimas | first3 = Nancy G | authorlink3 = Nancy Klimas
| last4 = Levine | first4 = Susan | authorlink4 = Susan Levine
| last5 = Felsenstein | first5 = Donna | authorlink5 = Donna Felsenstein
| last6 = Bateman | first6 = Lucinda | authorlink6 = Lucinda Bateman
| last7 = Peterson | first7 = Daniel L | authorlink7 = Daniel Peterson
| last8 = Gottschalk | first8 = C Gunnar | authorlink8 = Gunnar Gottschalk
| last9 = Schultz | first9 = Andrew F | authorlink9 = Andrew Schultz
| last10 = Che | first10= Xiaoyu | authorlink10= Xiaoyu Che
| last11 = Eddy | first11= Meredith L | authorlink11= Meredith Eddy
| last12 = Komaroff | first12= Anthony L | authorlink12= Anthony Komaroff
| last13 = Lipkin | first13= W Ian | authorlink13= Ian Lipkin
| title = Distinct plasma immune signatures in ME/CFS are present early in the course of illness
| journal = Science Advances | volume = 1 | issue = 1
| date = 1 February 2015
| url = http://advances.sciencemag.org/content/1/1/e1400121
}}</ref>


<ref name="Hvidberg2015">{{citation
[[Exercise]], especially GET, can harm an ME/CFS patient further.  
| last1 = Hvidberg | first1 = Michael Falk | authorlink1 = Michael Falk Hvidberg
| last2 = Brinth | first2 = Louise Schouborg | authorlink2 = Louise Schouborg Brinth
| last3 = Olesen | first3 = Anne V | authorlink3 = Anne V Oleson
| last4 = Petersen | first4 = Karin D | authorlink4 = Karin Peterson
| last5 = Ehlers | first5 = Lars | authorlink5 = Lars Ehlers
| title = The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)
| journal = PLoS One
| date = 6 Jul 2015
| doi = 10.1371/journal.pone.0132421
| url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132421
}}</ref>


<ref name="ICC2011criteria">{{citation
*[[Jennifer Brea]] walked home from her Neurologist's office and became [[severe and very severe ME|wheelchair-bound]].
| last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].  
| last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
| last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir
*[[Maik Speedy|Dr Maik Speedy]] was also seriously injured by GET and has been bedbound since.
| last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas
*British MP [[Brynmor John]] collapsed outside the House of Commons gym in 1998 and died, as a result of following his doctor's advice to exercise back to health.
| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick
| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell
| last7 = Staines | first7 = D | authorlink7 = Donald Staines
| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles
| last9 = Speight | first9 = N | authorlink9 = Nigel Speight
| last10 = Vallings | first10= R | authorlink10= Rosamund Vallings
| last11 = Bateman | first11= L | authorlink11= Lucinda Bateman
| last12 = Baumgarten-Austrheim | first12= B | authorlink12= Barbara Baumgarten-Austrheim
| last13 = Bell | first13= DS | authorlink13= David Bell
| last14 = Carlo-Stella | first14= N | authorlink14= Nicoletta Carlo-Stella
| last15 = Chia | first15= J | authorlink15= John Chia
| last16 = Darragh | first16= A | authorlink16= Austin Darragh
| last17 = Jo | first17= D | authorlink17= Daehyun Jo
| last18 = Lewis | first18= DP | authorlink18= Donald Lewis
| last19 = Light | first19= AR | authorlink19= Alan Light
| last20 = Marshall-Gradisnik | first20= S | authorlink20= Sonya Marshall-Gradisnik
| last21 = Mena | first21= I | authorlink21= Ismael Mena
| last22 = Mikovits | first22= JA | authorlink22= Judy Mikovits
| last23 = Miwa | first23= K | authorlink23= Kunihisa Miwa
| last24 = Murovska | first24= M | authorlink24= Modra Murovska
| last25 = Pall | first25= ML | authorlink25= Martin Pall
| last26 = Stevens | first26= SR | authorlink26= Staci Stevens
| title = Myalgic encephalomyelitis: International Consensus Criteria
| journal = Journal of Internal Medicine | volume = 270 | issue = 4 | page = 327–338
| date = 22 August 2011
| pmid = 21777306 | doi = 10.1111/j.1365-2796.2011.02428.x
| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/full
}}</ref>


<ref name="IOM2015MECFS">{{citation
=== Claims of recovery and cures ===
| last1 = Institute of Medicine (USA)
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref name="treatments">{{Cite web|url=https://www.cdc.gov/me-cfs/treatment/index.html | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Treatment | last = | first = | date = 2018-07-03 | website = [[Centers for Disease Control and Prevention]]|language=en-us|archive-url=|archive-date=|access-date=2021-11-22}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF) which is not the result of the neurological illness CFS. Some people misdiagnosed and "recovered" from CFS most likely had CF which can be caused by many illnesses, diseases, and drug therapies or a bad year or two perhaps with [[mononucleosis]] followed by a bout or two of [[influenza]]. These individuals were experiencing a proper immune response whereas ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref name="etiology">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html | title = Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html | title = IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html | title = Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-12 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-09-07}}</ref>
| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| publisher = The National Academies Press | location = Washington, DC, USA
| date = 10 February 2015
| isbn = 978-0-309-31689-7
| url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
}}</ref>


<ref name="Johnson20130706">{{citation
Additionally, there have been media reports of some professional or amateur athletes diagnosed with CFS that recovered in a relatively short period of time after [[rest]], [[:Category:Supplements|supplementation]], and [[:Category:Diets|diet changes]] <ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /> that may have had [[overtraining syndrome]],<ref name="spence" /> while some people with [[Addison's disease]] (adrenal failure) are erroneously diagnosed with CFS.<ref name="ICP2011primer" /><ref name="Carruthers, 2003" />
| last1 = Johnson | first1 = Cort | authorlink1 = Cort Johnson
| title = ME/CFS Prognosis
| journal = Health Rising
| date = 6 July 2013
| url = http://www.cortjohnson.org/about-chronic-fatigue-syndrome-mecfs/prognosis/
}}</ref>


<ref name="JoyceJ1997prog">{{citation
== Notable studies ==
| last1 = Joyce | first1 = J | authorlink1 = J Joyce
*[[Pathways to prevention report]] (P2P)
| last2 = Hotopf | first2 = M | authorlink2 = Matthew Hotopf
*[[Institute of Medicine report]]
| last3 = Wessely | first3 = Simon | authorlink3 = Simon Wessely
*[[PACE trial]] is a highly criticized UK trial designed by psychiatrists to promote [[GET]] and [[CBT]] as therapy which is deemed harmful and useless for ME/CFS patients by many clinicians, researchers, patients, and advocates.
| title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review
| journal = QJM | volume = 90 | issue = 3
| date = 1 March 1997
| pmid = 9093600 | doi = 10.1093/qjmed/90.3.223
| url = http://qjmed.oxfordjournals.org/content/90/3/223.long
}}</ref>


== Continuing education (CME and CE) ==
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059 Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059 | title = Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS | last = Bateman | first = Lucinda | authorlink=Lucinda Bateman|publisher=Michigan State Medical Society|via=On-Demand Webinars|archive-url=|archive-date=|access-date=2019-02-25}}</ref> (CME)
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060 Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS.]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060 | title = Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS. | last=Bateman | first = Lucinda | authorlink=Lucinda Bateman|website=Michigan State Medical Society|via=On Demand Webinars|archive-url=|archive-date=|access-date=2019-02-25}}</ref> (CME)
* [https://www.medscape.org/viewarticle/907632?src=acdmpart_cdc Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In]<ref>{{Cite web|url=https://www.medscape.org/viewarticle/907632?src=acdmpart_cdc | title = Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In | last = Bateman | first = Lucinda | authorlink=Lucinda Bateman | last2 = Azar | first2 = Natalie | authorlink2 = Natalie Azar | date = |publisher=Medscape|archive-url=|archive-date=|access-date=2019-02-25 | last3 = Klimas | first3 = Nancy | authorlink3 = Nancy Klimas | last4 = Montoya | first4 = Jose | authorlink4 = Jose Montoya}}</ref> (CME/CE)
* [https://www.unrest.film/cme Watch ''Unrest'' and Receive Continuing Medical Education (CME /CE) Credit]<ref>{{Cite web|url=https://www.unrest.film/cme | title = Unrest Continuing Medical Education Program | date = |website=UNREST|language=en-US | last = Indiana University School of Medicine | last2 = American Medical Women's Association|archive-url=|archive-date=|access-date=2019-02-25}}</ref>


==History==
*[[Osler's Web]] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain]] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.


<ref name="MEACTIONpacepetition">{{citation
=== Deaths of ME/CFS patients ===
| last1 = #MEAction | authorlink1 = #MEAction
*[[Causes of death]]
| title = Petition: Misleading Claims Should Be Retracted
*[[Suicide]]
| journal = #MEAction
| date = Oct 2015
| url = http://my.meaction.net/petitions/pace-trial-needs-review-now
}}</ref>


<ref name="MEACTION20160313openletr">{{citation
'''Death certificates with ME or CFS'''
| last1 = #MEAction | authorlink1 = #MEAction
*[[Merryn Crofts]]' death is attributed to ME.
| title = 24 organisations in 14 countries tell QMUL: Release the PACE data
*[[Sophia Mirza]]'s death is attributed to CFS.
| date = 13 Mar 2016
| url = http://www.meaction.net/2016/03/13/24-organisations-in-14-countries-tell-qmul-release-pace-data/#comment-2518
}}</ref>


<ref name="MEASSUK20150529survey">{{citation
In the UK, United States, and Australia there are further reports of loved ones who have died due to ME/CFS.<ref>{{Cite news | url=https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ | title = Not, sadly, the first|work=New Scientist|access-date=2018-08-23|language=en-US}}</ref> See Editor's Note<ref>{{Cite news | url=https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ | title = First official UK death from chronic fatigue syndrome | last = Hooper | first = Rowan | date = 2006-06-16|work=New Scientist|access-date=2018-08-23|archive-url=|archive-date=|language=en-US}}</ref>
| last1 = ME Association (UK) | authorlink1 = ME Association
| date = 29 May 2015
| title = Our CBT, GET and Pacing Report calls for major changes to therapies offered for ME/CFS
| url = http://www.meassociation.org.uk/2015/05/23959/
}}</ref>


<ref name="NakatomiY2014">{{citation
==See also==
| last1 = Nakatomi | first1 = Yasuhito | authorlink1 = Yasuhito Nakatomi
*[[List of systematic reviews about ME/CFS/SEID]]
| last2 = Mizuno | first2 = Kei | authorlink2 = Kei Mizuno
*[[International Consensus Criteria]] - with primer for clinicians
| last3 = Ishii | first3 = Ishii | authorlink3 = Akira Ishii
*[[misdiagnosis of myalgic encephalomyelitis and chronic fatigue syndrome]]
| last4 = Yasuhiro | first4 = Wada | authorlink4 = Yasuhiro Wada
*[[Fibromyalgia]]
| last5 = Masaaki | first5 = Tanaka | authorlink5 = Masaaki Tanaka
*[[PACE trial]]
| last6 = Shusaku | first6 = Tazawa | authorlink6 = Shusaku Tazawa
*[[Primer for patients]]
| last7 = Kayo | first7 = Onoe | authorlink7 = Kayo Onoe
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]
| last8 = Sanae | first8 = Fukuda | authorlink8 = Sanae Fukuda
==Learn more==
| last9 = Joji | first9 = Kawabe | authorlink9 = Joji Kawabe
'''Films'''
| last10 = Kazuhiro | first10= Takahashi | authorlink10= Kazuhiro Takahashi
*''[[Forgotten Plague]]'' is a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD purchase]. (2015)
| last11 = Yosky | first11= Kataoka | authorlink11= Yosky Kataoka
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
| last12 = Susumu | first12= Shiomi | authorlink12= Susumu Shiomi
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[myalgic encephalomyelitis|ME]], directs. (2017)
| last13 = Kouzi | first13= Yamaguti | authorlink13= Kouzi Yamaguti
[[File:Unrest.jpg|400px|thumb|center]]
| last14 = Masaaki | first14= Inaba | authorlink14= Masaaki Inaba
| last15 = Hirohiko | first15= Kuratsune | authorlink15= Hirohiko Kuratsune
| last16 = Yasuyoshi | first16= Watanabe | authorlink16= Yasuyoshi Watanabe
| title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study
| journal = Journal of Nuclear Medicine | volume = 2014 Jun;55(6) | page = 945-50
| date = 24 Mar 2014
| pmid = 24665088 | doi = 10.2967/jnumed.113.131045
| url = http://jnm.snmjournals.org/content/55/6/945.long
}}</ref>


'''ME/CFS organization's and researcher's material'''
*[https://www.youtube.com/watch?v=hRdn4A2SGic Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]<ref>{{Cite web|url=https://www.youtube.com/watch?v=hRdn4A2SGic | title = Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education | last = Iskander | first=John | last2 = Komaroff | first2 = Anthony | date = 2016-02-17 | website = YouTube|publisher=Centers for Disease Control and Prevention (CDC)|archive-url=|archive-date=|access-date=}}</ref>
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref>{{Cite news | url=https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view | title = Caregivers Guide to ME|type=pdf | last = | first = | date = 2018 | work=Google Docs|access-date=2018-08-23|archive-url=|archive-date=|publisher=#MEAction}}</ref>
*[https://www.massmecfs.org/images/pdf/Primer_2014.pdff IACFS/ME Primer for Clinical Practitioners - 2014 Edition]<ref name="IACFSME2014primer" />
*[http://www.meassociation.org.uk/2014/07/our-purple-booklet-clear-clinical-guidance-and-the-latest-research-all-wrapped-up-in-52-pages/ ME Association clinical guidance]<ref name="MEASSUKprimer2013">{{Cite web | last1 = Shepherd | first1 = C | authorlink1 = Charles Shepherd | last2 = Chaudhuri | first2 = A | authorlink2 = Abhijit Chaudhuri | title = ME/CFS/PVFS An Exploration of the Key Clinical Issues ('Purple Booklet') | date = 2013| url = http://www.meassociation.org.uk/wp-content/uploads/2011/01/pruple-booklet-front-cover.jpg }}</ref>
*[http://youtu.be/c2vIQ92wU9Y ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=c2vIQ92wU9Y&feature=youtu.be | title = ME/CFS Diagnosis and Name with Dr. Nancy Klimas | last = Klimas | first = Nancy | date = 2014-06-21 | website = YouTube|publisher=ME/CFS Community|archive-url=|archive-date=|access-date=}}</ref>
*[http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf ME/CFS Treatment Resource Guide for Practitioners by A Martin Lerner, MD]<ref name="LernerPrimer2011">{{Cite web | last1 = Lerner | first1 = AM | authorlink1 = A Martin Lerner| title = ME/CFS Treatment Resource Guide for Practitioners| date = 2011| url = http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf }}</ref>
*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf Myalgic Encephalomyelitis - Adult & Pediatric - International Consensus Criteria Primer for Medical Practitioners]<ref name="ICP2011primer" />
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]<ref name="whatis">{{Cite news | url=https://www.omf.ngo/what-is-mecfs/ | title = What is ME/CFS?|website=[[Open Medicine Foundation]]|access-date=2018-08-23|language=en-US}}</ref>


<ref name="openletrLANCET2">{{citation
'''[[Patient mental health]]'''
| last1 = Davis | first1 = Ronald W | authorlink1 = Ronald Davis
| last2 = Edwards | first2 = Jonathan C W | authorlink2 = Jonathan Edwards
| last3 = Jason | first3 = Leonard A | authorlink3 = Leonard Jason
| last4 = Levin | first4 = Bruce | authorlink4 = Bruce Levin
| last5 = Racaniello | first5 = Vincent R | authorlink5 = Vincent Racaniello
| last6 = Reingold | first6 = Arthur L | authorlink6 = Arthur Reingold
| last7 = Ablashi | first7 = Dharam V | authorlink7 = Dharam Ablashi
| last8 = Baraniuk | first8 = James N | authorlink8 = James Baraniuk
| last9 = Barcellos | first9 = Lisa F | authorlink9 = Lisa Barcellos
| last10 = Bateman | first10= Lucinda | authorlink10= Lucinda Bateman
| last11 = Bell | first11= David S | authorlink11= David Bell
| last12 = Bested | first12= Alison C | authorlink12= Alison Bested
| last13 = Broderick | first13= Gordon | authorlink13= Gordon Broderick
| last14 = Chia | first14= John | authorlink14= John Chia
| last15 = Chu | first15= Lily | authorlink15= Lily Chu
| last16 = Enlander | first16= Derek | authorlink16= Derek Enlander
| last17 = Fletcher | first17= Mary Ann | authorlink17= Mary Ann Fletcher
| last18 = Friedman | first18= Kenneth | authorlink18= Kenneth Friedman
| last19 = Kaufman | first19= David L | authorlink19= David Kaufman
| last20 = Klimas | first20= Nancy | authorlink20= Nancy Klimas
| last21 = Lapp | first21= Charles W | authorlink21= Charles Lapp
| last22 = Levine | first22= Susan | authorlink22= Susan Levine
| last23 = Light | first23= Alan R | authorlink23= Alan Light
| last24 = Marshall-Gradisnik | first24= Sonya | authorlink24= Sonya Marshall-Gradisnik
| last25 = Medveczky | first25= Peter G | authorlink25= Peter Medveczky
| last26 = Nahle | first26= Zaher | authorlink26= Zaher Nahle
| last27 = Oleske | first27= James M | authorlink27= James Oleske
| last28 = Podell | first28= Richard N | authorlink28= Richard Podell
| last29 = Shepherd | first29= Charles | authorlink29= Charles Shepherd
| last30 = Snell | first30= Christopher R | authorlink30= Christopher Snell
| last31 = Speight | first31= Nigel | authorlink31= Nigel Speight
| last32 = Staines | first32= Donald | authorlink32= Donald Staines
| last33 = Stark | first33= Philip B | authorlink33= Philip Stark
| last34 = Stein | first34= Eleanor | authorlink34= Eleanor Stein
| last35 = Swartzberg | first35= John | authorlink35= John Swartzberg
| last36 = Tompkins | first36= Ronald G | authorlink36= Ronald Tompkins
| last37 = Underhill | first37= Rosemary | authorlink37= Rosemary Underhill
| last38 = Vallings | first38= Rosamund | authorlink38= Rosamund Vallings
| last39 = Van ElZakker | first39= Michael | authorlink39= Michael Van ElZakker
| last40 = Weir | first40= William | authorlink40= William Weir
| last41 = Zinn | first41= Marcie L | authorlink41= Marcie Zinn
| last42 = Zinn | first42= Mark A | authorlink42= Mark Zinn
| title = An open letter to the Lancet - again
| date = 10 Feb 2016
| website = Virology Blog
| url = http://www.virology.ws/2016/02/10/another-request-for-data-from-the-pace-trial/
}}</ref>


<ref name="StanfordMed20141028">{{citation
:Patients who were deemed as suffering from mental health rather than a biological illness:
| last1 = Montoya | first1 = José G | authorlink1= Jose Montoya
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
| title = Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after; she then died of ME.
| journal = Radiology | volume = 274 | issue = 2
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become [[paralysis|paralyzed]] and mute and was let go in the deep end of a pool to make him swim, and put on a scary theme park ride to scare him into moving.
| date = Feb 2015
| url = http://pubs.rsna.org/doi/abs/10.1148/radiol.14141079
}}</ref>


<ref name="TullerD20141124brain">{{citation
'''More mental health information'''
| last1 = Tuller | first1 = David | authorlink1 = David Tuller
*ME/CFS is not [[depression]]. It causes a lack of energy, not a lack of desire to do activities.<ref name="Griffith, 2008">{{Cite journal | last1 = Griffith | first1 = J.P. | authorlink1 = | last2 = Zarrouf | first2 = F.A. | authorlink2 = | title = A Systematic Review of Chronic Fatigue Syndrome: Don’t Assume It’s Depression| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292451/| pmc =2292451| journal = Primary Care Companion to The Journal of Clinical Psychiatry | volume = 10 | issue = 2 | page = 120–128| date = 2008 | pmid = 18458765 | doi = 10.4088/pcc.v10n0206 }}</ref><ref name="Hawk, 2006">{{Cite journal | last1 = Hawk | first1 = C | authorlink1 = | last2 = Jason | first2 = L | authorlink2 = Leonard Jason | last3 = Torres-Harding | first3 = S | authorlink3 = Susan Torres-Harding| title = Differential diagnosis of chronic fatigue syndrome and major depressive disorder | journal = International Journal of Behavioral Medicine | volume = 13 | issue = 3 | page = 244-51 | date = 2006 | pmid = 17078775 | doi = 10.1207/s15327558ijbm1303_8
| title = Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder
| url = http://www.healthrising.org/wp-content/uploads/2014/04/Hawk.-Jason.-Differential-Diagnosis-of-Chronic-Fatigue-Syndrome-and-Major-Depressive-Disorder.pdf }}</ref><ref name="myhill">{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences | title = CFS or depression - what are the differences - DoctorMyhill|last =Myhill | first =Sarah | authorlink = Sarah Myhill|website=DrMyhill|language=en|access-date=2018-08-23}}</ref>
| journal = New York Times | volume = Well Blogs
| date = 24 Nov 2014
| url = http://well.blogs.nytimes.com/2014/11/24/brains-of-people-with-chronic-fatigue-syndrome-offer-clues-about-disorder/
}}</ref>  


<ref name="TwiskF2015">{{citation
'''Research'''
| last1 = Twisk | first1 = Frank NM | authorlink1 = Frank Twisk
* 2015, [[Institute of Medicine report]] (IOM Report)
| last2 = Geraghty | first2 = Keith J | authorlink2 = Keith Geraghty
| title = Deviant Cellular and Physiological Responses to Exercise in Myalgic Encephalomyelitis and Chronic Fatigue Syndrome
| journal = Jacobs Journal of Physiology | volume = 2015, 1(2): 007
| date = 11 Jul 2015
| url = http://www.jacobspublishers.com/images/Physiology/J_J_Physiology_1_2_007.pdf
}}</ref>


<ref name="Phoenix20160222Norway2012">{{citation
* 2016, [http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598 The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem]<ref name="Edwards2016">{{Cite journal | last1 = Edwards | first1 = JCW | authorlink1 = Jonathan Edwards | last2 = McGrath | first2 = S | authorlink2 = Simon McGrath | last3 = Baldwin | first3 = A | authorlink3 = Adrian Baldwin | last4 = Livingstone | first4 = M | authorlink4 = Mark Livingstone | last5 = Kewley | first5 = A | authorlink5 = Andrew Kewley | title = The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem | journal = Fatigue: Biomedicine, Health & Behavior | volume = 4 | issue = 2 | pages = 63–69 | date = 2016-04-02 | doi = 10.1080/21641846.2016.1160598 | url = http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598}}</ref>
| title = Norwegian patient survey: Experiences of therapeutic approaches (2012)
*2018, The CDC based it's updated [https://www.cdc.gov/me-cfs/index.html ME/CFS page] based on the IOM Report.
| journal = Phoenix Rising Forum
*[[Notable studies]]
| date = 22 Feb 2016
'''Articles and blogs'''
| url = http://forums.phoenixrising.me/index.php?threads/norwegian-patient-survey-experiences-of-therapeutic-approaches-2012-update.43193/
* Feb 21, 2019 [https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/ Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?]<ref>{{Cite web|url=https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/ | title = Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined? | last = Muirhead | first=Nina | authorlink=Nina Muirhead | date = Feb 21, 2019 | website = Royal College of Surgeons|language=en|archive-url=|archive-date=|access-date=2019-02-22}}</ref>
}}</ref>  


<ref name="viroblogMECFS">{{citation
==References==
| title = List of ME/CFS articles published at Virology Blog
<references>
| url = http://www.virology.ws/mecfs/  
<ref name="viroblogMECFS">{{Cite web | title = List of ME/CFS articles published at Virology Blog| url = http://www.virology.ws/mecfs/ }}</ref>
}}</ref>
</references>
</references>
[[Category:Primers]]
[[Category:Primers]]

Latest revision as of 09:38, December 7, 2023

Chronic fatigue syndrome (CFS) is also known as myalgic encephalomyelitis (ME) or ME/CFS. There are many clinical and research definitions, which creates confusion for doctors, researchers, and patients.

It is worth noting that chronic fatigue (without the "syndrome") is a not a disease in and of itself, but a symptom of many diseases and drug therapies. This term is not interchangeable with CFS, ME, or ME/CFS.

What is ME/CFS By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)

The core ME/CFS symptoms are: chronic fatigue (CF); post-exertional malaise (PEM); unrefreshing sleep/sleep problems; and cognitive impairment/brain fog and/or orthostatic intolerance (OI).[1][2] A person with ME is likely to have other symptoms as well.[3] Systemic Exertion Intolerance Disease (SEID), an ME/CFS criteria, allows for a patient to be diagnosed with the minimum core symptoms [4][2]. The Canadian Consensus Criteria (CCC) requires the core symptoms along with additional neurological, autonomic, neuroendocrine, and immune symptoms.[5] The International Consensus Criteria (ICC) is used to diagnose myalgic encephalomyelitis (ME) which requires the core symptoms and neurological, immune/gastrointestinal/genitourinary impairment, and energy metabolism/ion transport impairment symptoms for a diagnosis.[6]

Although the Fukuda[7] and the Oxford Criteria[8] have been used for diagnosing CFS, they are broader criteria, making misdiagnosis a concern.[9][10][7][11][12] There have been media reports of athletes diagnosed with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes;[13][14][15][16] these athletes may have had overtraining syndrome (which has the symptom of CF) and not ME or CFS.[17] Some people with anemia, allergies, idiopathic chronic fatigue or other fatiguing illnesses are erroneously diagnosed with CFS.[5]

The acronym ME/CFS is widely used in research, by clinicians, patient organizations, and patients.

"The most common overlapping condition with ME/CFS is fibromyalgia."[18][19] While some have posited ME/CFS and fibromyalgia are variants of the same illness, Benjamin Natelson, MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.[20]

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. Graded exercise therapy (GET) and cognitive behavioral therapy (CBT) are used in the UK inappropriately for treating ME/CFS. As of 2021 the GET has been scrapped in the UK [1].

The Centers for Disease Control and Prevention (CDC) website states "ME/CFS is a biological illness, not a psychologic disorder" and impacts multiple body systems.[21] The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity[1] and says ME/CFS is a "disabling and complex disease."[22] 

Diagnostic Algorithm for SEID's minimum ME/CFS core symptoms

Disease onset and course of illness[edit | edit source]

ME/CFS can begin from many acute/sudden[23] events: usually viral or bacterial infections, but also trauma, surgery or childbirth, allergic reaction, and stress.[24] There is also a gradual onset in some people,[23][25] that is not attributed to any one event. Occasionally, ME/CFS has been triggered by environmental toxins or the receipt of an immunizing injection.[26] Some say that the disease ME always has an acute/sudden infectious onset.[27]

The disease ME/CFS is often diagnosed when a person does not recover from a flu-like illness, mononucleosis or another herpesvirus, Q fever, an unidentified virus, or other infection, and meets one or more diagnostic criteria for either ME, CFS, or ME/CFS.[28][29] Patients experience numerous symptoms and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.[30][31][32]

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, immune system changes, stress affecting body chemistry, changes in energy production, and a possible genetic link.[33][21] The CDC notes there are abnormalities with the immune system, cellular metabolism, neuroendocrine disturbances, and blood pressure or heart rate regulation.[21]

Not a mental health disorder[edit | edit source]

In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."[21]

No clear evidence that ME/CFS is contagious[edit | edit source]

Infectious episodes have led to outbreaks over the years and 72% of ME/CFS patients report an onset of a viral or bacterial infection.[34] Nowadays, the vast majority of ME/CFS cases are sporadic rather than epidemic, and although some outbreaks have been caused by known viruses - such as the SARS pandemic and COVID-19 - there is no clear evidence that sporadic ME/CFS cases are contagious.[35]

Families, partners, and friends do not report contracting ME/CFS from someone with the disease nor do patients report passing it on to others.[36] However, Underhill and O'Gorman (2006) researched 219 patients with ME/CFS, and concluded that close household contact and genetics were both risk factors for CFS, finding 3.2% of spouses/partners of those with CFS also had the illness.[37] This was a higher prevalence than all genetic relatives except children of patients. Because ME/CFS can run in families, a genetic link is a line of research recommended by the CDC.[38]

Michael Sikora and collaborators at the Open Medicine Foundation hope that their research on the role of T cells and immune-related genes will help address "whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system".[39]

Blood donation and organ transplant[edit | edit source]

Patients with ME/CFS are banned from donating blood or tissues in the UK by the UK's National Health Service, including patients who have recovered.[40][41] In the United States a temporary ban on donations from ME/CFS patients was put in place due to the research of XMRV as being the infectious trigger of CFS[42][43] and that patients carried the virus.[42] Two papers on XMRV were retracted as it was a laboratory contamination.[44][45] Currently the US American Red Cross no longer have statements barring transfusions or transplants from ME/CFS patients, but patients are expected to be in "good health" which would exclude most.[46] Patient charities discouraged ME/CFS patients from donating blood,[47] but the American Association of Blood Banks advises to either accept or defer donors based on "clinical judgment of the donor's health status".[48]

New Zealand bans blood donation from anyone with ME/CFS.[49] Australia has a prohibition on blood donation as a precaution because it has not been established if ME/CFS could be caused by a transmissible infection.[50]

Mini-Docs[edit | edit source]

By Jen Brea/TED (2016)

What happens when you have a disease doctors can't diagnose By Jen Brea/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her illness, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.[51][52]

By Veronica Weber/Palo Alto Online (2015)

Invisible Illness - Stories of Chronic Fatigue Syndrome By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by Chronic Fatigue Syndrome - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online[53]

By Dr. David Kaufman/Unrest (2018)

Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome By Dr. David Kaufman/Unrest

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is part of the Unrest Continuing Education module, made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch Unrest online for free and receive Continuing Education credit.[54]

Epidemiology[edit | edit source]

In the United States, 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."[2] Some CFS patients can work with job accommodations but 1/3 to 1/2 become unemployed and many rely on SSDI/SSI.[55][56][57]

All races and cultures are afflicted with ME/CFS.[58][59] Children and adolescents are also diagnosed.[60][61]
Like many autoimmune and neuro-immune diseases where mostly women are afflicted,[62] the ME/CFS female/male patient ratio per Capelli et al. is 6:1[63] while the CDC states 4:1.[59]
Pediatric ME/CFS is defined by the CDC[64] and the National Academy of Medicine (NAM)[65] although it is usually diagnosed in adults. [22] "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."[66] The prognosis in adolescents is considered to be better than in adults.[67][35] Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.[68][2][5][6]
"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."[69] 25% of ME/CFS patients are housebound or bedbound at some point in their illness.[70][71] 90% of patients are undiagnosed.[22]
The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.[72] The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.[72][73]

Evidence of a disease[edit | edit source]

Symptoms[edit | edit source]

Symptom presentation varies enormously between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.[74] There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

.[1]

Rosa age 25 in 1986 and mildly ill with ME/CFS's core symptoms. In 2015 the SEID criteria were released. Rosa read about PEM and how it is delayed and makes ME/CFS symptoms like CF, OI, and cognition worse. Her life since age 17 fell into place as she never connected her worsening symptoms with increased physical or mental activity 24-72 hours prior. She believes not understanding PEM made her illness worsen over the years and is now disabled meeting the CCC with PEM"option"
Brian Vastag is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment
I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.[75]
First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak, etc. #TwoFacesofME[76]
#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.[77]
  • Post-exertional malaise (PEM) is the hallmark symptom of ME/CFS. After physical or mental exertion (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)[3][78][79] there is a payback of worsening ME/CFS symptoms which can be delayed 24-72 hours or more[80][81][82] and can last 24 hours and even days, weeks, or months.[83][84] The patient will experience even greater fatigue as well as exasperate the flu-like symptoms and body pain. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.[3][78][79] Regarding PEM the CFIDS Association of America states:

This is a term which describes a symptom in which exercise or exertion can bring on malaise (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).[85]

Other possible symptoms[edit | edit source]

Comorbids[edit | edit source]

Government guides on symptoms[edit | edit source]

US Government guides on symptoms

Canada guides on symptoms

Biological abnormalities[edit | edit source]

Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the disease. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. While it is true that the disease is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the central nervous system, autonomic nervous system, immune system, and energy metabolism.[87] Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a biomarker of the illness, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the illness, it cannot yet be determined whether these are a cause or consequence of the illness.

Notable studies[edit | edit source]

  • 2014, Neuroinflammation Japanese Neuroinflammation study,[89] Younger's Leptin study[90]
  • 2014, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome[91]

Bilateral white matter atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA may serve as a biomarker for CFS.

Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: Michael Zeineh

Causes & triggers[edit | edit source]

Epidemiology[edit | edit source]

Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the illness used.[6] In the US, estimates range between 836,000 and 2.5 million people with the illness, though true numbers are under-reported. It is estimated that 84-91% of people with the illness remain undiagnosed.[87]

  • Level of disability (eg, Norwegian study HRQoL by Hvidberg, 2015) suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)[94]

Severely ill patients[edit | edit source]

Considerable variation exists in the severity of the illness. The International Consensus Criteria lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

  • Mild = 50% reduction in pre-illness activity levels
  • Moderate = mostly housebound
  • Severe = mostly bedridden
  • Very Severe = totally bedridden, and needing help with basic functions.

At least 25% of people with ME/CFS are bed-bound or housebound, often for years or even decades, so are largely an invisible population.[87] So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The Open Medicine Foundation's ME/CFS Severely Ill, Big Data Study will be the first in-depth study of people with a severe form of ME/CFS.

Notable patients with severe ME/CFS include Whitney Dafoe, Karina Hansen (had been sanctioned), Laura Hillenbrand, Tom Kindlon, Doctor Speedy, Naomi Whittingham, Jen Brea, and Emma Shorter.

Though uncommon, there have been instances of deaths which have been attributed to the disease. (See: Sophia Mirza and Merryn Crofts.) Also, see Vanessa Li and Lynn Gilderdale.

Centers for Disease Control and Prevention (CDC)[edit | edit source]

  • Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.[97][98]
  • Feb 25, 2019, Dr. Elizabeth Unger, Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between Medscape and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: Chronic Fatigue Syndrome: It's Real, and We Can Do Better.[99]

MEAction input

Tests[edit | edit source]

Treatments[edit | edit source]

There are currently no FDA approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.[100] There are many potential treatments, though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

Drugs[edit | edit source]

Ampligen

Two treatments that have garnered much attention are Ampligen, produced by AIM ImmunoTech, and Rituximab. Many people have reported benefit from Ampligen;[101]

Attempts to obtain FDA approval for Ampligen in the United States have failed so it is unavailable to many.[102] Argentina approved the use of Ampligen for severe ME/CFS in 2016.[103][104] Also in 2016, it was made available on a limited basis in Europe.[105] In July of 2018, AIM ImmunoTech announced the expansion of its Treatment Protocol/Expanded Access Programs (compassionate use) for ME/CFS in the United States, known as AMP-511, to new patients.[106] AMP-511 "will allow treatment of up to 100 ME/CFS patients at any one time at approved clinical infusion therapy sites."[107] The most recent Ampligen trial was published in 2020.[108]

Rituximab, a lymphoma drug, had shown promising results in initial trials in Norway,[109] and there were groups crowdsourcing funding for further trials in other countries. In 2017, Drs. Øystein Fluge and Olav Mella announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab.[110] A phase III trial published in 2019 showed Rituximab did not improve ME/CFS.[111]

Jarred Younger announced he will be undertaking a trial of low dose naltrexone (LDN) in ME/CFS.[112]

Treating other conditions[edit | edit source]

Different forms of OI are treated with beta-blockers (Metopropol), Fludrocortisone (Florinef), and Pyridostigmine.[113] When treating other diseases, illnesses, and conditions, and ME/CFS comorbidities or overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are sensitive to medications.[114] The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the central nervous system, such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."[114] For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI.[114][5]

Exercise as treatment[edit | edit source]

Jennifer Brea is an American who was studying at Harvard; while on a trip to Kenya she became very ill with what would eventually be diagnosed as ME/CFS. Brea began experiencing neurological problems. Her neurologist diagnosed her with "conversion disorder" (hysteria). When walking home from his office, she collapsed. Jen then needed to use a wheelchair, keeping her legs up due to POTS as her blood pools into her legs

Two common treatment recommendations for ME/CFS are GET and CBT. These treatments are based on the disproven hypothesis that the illness might have begun with a viral infection but has been perpetuated by deconditioning from lack of activity, and fear and avoidance of activity. GET and CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that are claimed to result in avoidance of activity, and by increasing fitness through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which provides evidence that exercise is harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,[115] which is consistent with other patient surveys.[116]

The PACE trial, published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.[117] The study was the subject of a series of investigative pieces by journalist David Tuller in late 2015, that were highly critical of the trial.[118] A petition signed by almost 12,000 ME/CFS patients and allies,[119] and an open letter signed by 42 ME/CFS experts from around the world,[120] were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.[121] To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of post-exertional malaise (PEM), which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary people, the adverse effects of exercise cannot be said to be due to deconditioning.[122][citation needed][citation needed]

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

Anaerobic threshold, use of heart rate monitors for activity and pacing. Analeptic, not aerobic. Energy envelope/pacing - people do better if stay within their envelope than to push to increase activity

Graded exercise therapy & Cognitive behavioral therapy[edit | edit source]

Emma Shorter, is a citizen of Scotland. Here, she gives testimony before Parliament's Petitions Committee on GET and how it put her in a wheelchair

GET and CBT are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the disproven biopsychosocial model of ME/CFS, backed up by the flawed PACE trial which used the flawed Oxford criteria to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

Exercise, especially GET, can harm an ME/CFS patient further.

Claims of recovery and cures[edit | edit source]

Charlatans claim they can cure CFS (per the CDC "there is no cure"[123]) when in reality they may be able to treat chronic fatigue (CF) which is not the result of the neurological illness CFS. Some people misdiagnosed and "recovered" from CFS most likely had CF which can be caused by many illnesses, diseases, and drug therapies or a bad year or two perhaps with mononucleosis followed by a bout or two of influenza. These individuals were experiencing a proper immune response whereas ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.[21][124][125]

Additionally, there have been media reports of some professional or amateur athletes diagnosed with CFS that recovered in a relatively short period of time after rest, supplementation, and diet changes [13][14][15][16] that may have had overtraining syndrome,[17] while some people with Addison's disease (adrenal failure) are erroneously diagnosed with CFS.[113][5]

Notable studies[edit | edit source]

Continuing education (CME and CE)[edit | edit source]

History[edit | edit source]

Deaths of ME/CFS patients[edit | edit source]

Death certificates with ME or CFS

In the UK, United States, and Australia there are further reports of loved ones who have died due to ME/CFS.[130] See Editor's Note[131]

See also[edit | edit source]

Learn more[edit | edit source]

Films

Forgotten Plague.jpeg
Unrest.jpg

ME/CFS organization's and researcher's material

Patient mental health

Patients who were deemed as suffering from mental health rather than a biological illness:
  • Karina Hansen is a young Danish woman taken from her family for 3 1/2 years due to Per Fink's insistence her ME was due to mental health issues.
  • Sophia Mirza was taken forcibly from her home to a mental hospital only to be returned shortly after; she then died of ME.
  • Ean Proctor was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end of a pool to make him swim, and put on a scary theme park ride to scare him into moving.

More mental health information

Research

Articles and blogs

References[edit | edit source]

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